Hall 2014.

Study characteristics
Patient sampling	Study design: case‐control study (1:3), age‐matched randomly selected from a larger cohort. Participants: pregnant women with an affected fetus or considered to be at high risk of fetal aneuploidy were recruited. Inclusion criteria: pregnant women at least 18 years of age who had signed an informed consent, and with singleton pregnancy. Exclusion criteria: fetal mosaicism.
Patient characteristics and setting	Number enrolled: more than 1000 pregnant women. Number available for 2 x 2 table: 64 pregnant women (subgroup of 6%). Setting: 6 centres. Western Institutional (WA, USA), Einstein Institutional (CA and MO, USA), Polish Mother’s Memorial Hospital Institutional (Polish), Bio Medical Research Institute of America (CA, USA), and the Mt. Sinai School of Medicine (NY, USA). Recruitment period: March to December of 2012. Ethnicity: not reported. Median gestational age (range): 16.0 (12.1 to 22.7) weeks. Maternal age: not reported. Relevant tests carried out prior to index test: ultrasonography (nuchal translucency measurement) and biochemical screening. Language of the study: English.
Index tests	gNIPT by TMPS (SNP‐based method) on Illumina Genome Analyzer IIx or HiSeq sequencer. Samples were amplified using 11,000‐plex or 19,488‐plex targeted polymerase chain reaction (targets included SNPs from chromosomes 13, 18, 21, X, and Y). Mean fetal fraction DNA (median; range): 12.1% (11.1%; 2.2% to 30.4%). 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 condition: T13. Reference standards: fetal karyotype of chorionic villi or amniotic fluid or genetic testing of the cord blood, buccal, saliva or products of conception.
Flow and timing	Blood samples were obtained prior to the invasive procedure (reference standard). gNIPT was a second‐tier test. About 932 samples were not selected for this case‐control study. 4/68 samples failed DNA quality threshold for low fetal fraction DNA (no gNIPT result). No repeated test reported.
Comparative
Aim to study	To determine how a single nucleotide polymorphism (SNP)‐ and informatics‐based non‐invasive prenatal aneuploidy test performs in detecting trisomy 13.
Funding source or sponsor of the study	Study funded by Natera, Inc. (involved in study design, data collection and analysis, decision to publish, and preparation of the manuscript).
Informations about the authors contacted	Authors were contacted on: 21 April 2016, and 27 May 2016. No reply received from the authors.
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?	No
Did the study avoid inappropriate exclusions?	No
		High	Low
DOMAIN 2: Index Test TMPS
Were the index test results interpreted without knowledge of the results of the reference standard?	Unclear
If a threshold was used, was it pre‐specified?	Yes
		Unclear	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?	No
		High