Jackson 2014.

Study characteristics
Patient sampling	Study design: prospective cohort study. Participants: pregnant women selected at high risk and low risk of fetal aneuploidy presenting for screening. Inclusion criteria: not reported. Exclusion criteria: not reported.
Patient characteristics and setting	Number enrolled: 1228 pregnant women screened at first‐trimester, including 1184 pregnant women with normal first‐trimester ultrasound and 44 with abnormal ultrasound. Number available for 2 x 2 table: 1161 pregnant women (subgroup of 95%). Setting: 1 centre. South Shore Hospital in USA. Recruitment period: June 2012 to January 2013. Ethnicity: not reported. Gestational age: not reported. Median maternal age: 31.5 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 TMPS (DANSR assay). Fetal fraction DNA: not reported. Blood samples for gNIPT were collected before reference standard. Cutpoint: not reported. Usually, Harmony™ prenatal test uses FORTE algorithm; positive if FORTE risk score ≥ 1%. Commercial test: Harmony™ Prenatal Test.
Target condition and reference standard(s)	Target conditions: T21, T18 and T13. Reference standards: fetal karyotype of chorionic villi or amniotic fluid, or medical record from birth.
Flow and timing	Blood samples were obtained prior to the invasive procedure (reference standard). gNIPT was a second‐tier test. 67/1228 samples excluded of 2 x 2 tables, including 7 women with other abnormal ultrasound, 14 women opted for CVS only without gNIPT, 32 women declined all testing and 14 samples failed after 2 attempts during sequencing process (no gNIPT result).
Comparative
Aim to study	To assess the performance of nuchal translucency measurement followed by gNIPT in the first‐trimester to screen for aneuploidy in a community‐based average‐risk population.
Funding source or sponsor of the study	Funding source not reported but 1 author is employed by Ariosa Diagnostics, Inc.
Informations about the authors contacted	Author was contacted on: 22 February 2016 and 15 March 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?	Unclear
Was a case‐control design avoided?	Unclear
Did the study avoid inappropriate exclusions?	Unclear
		Unclear	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?	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