de Robertis 2017.

Study characteristics
Patient Sampling	Study design: prospective observational study Recruitment: consecutive pregnant women undergoing routine first‐trimester screening for chromosomal abnormalities at the study centre were enrolled in the study Study start and end date: September 2013 to September 2015
Patient characteristics and setting	Setting: tertiary care facility (Di Venere‐Sarcone Hospital) Region(s) and country/countries from which participants were recruited: Bari, Italy Sample size: 5319 Study eligibility criteria: pregnant women with a viable singleton pregnancy and follow‐up data available. Cases of pregnancy termination or spontaneous fetal death where autopsy results were unavailable were excluded. Number of participants with the target condition: 33 Population type: unselected population Prior testing: not reported
Index tests	Type: two‐stage screening (data were only reported for first‐trimester scan): First‐trimester scan: Timing (weeks and days gestation): 11 to 14 weeks’ gestation Ultrasound scanning protocol: detailed Cardiac screening: extended Mode of examination: primary transabdominal, transvaginal if necessary Single or multiple operators: multiple Staff qualification and/or operator experience level: certified by the Fetal Medicine Foundation Second‐trimester scan: Data to construct 2 x 2 tables could not be extracted or derived from the report
Target condition and reference standard(s)	Target condition(s): major cardiac anomalies Definitions used for major and minor congenital abnormalities: not reported Reference standard (live birth): confirmation by fetal cardiologist and/or surgery Reference standard (fetal or neonatal demise): postmortem autopsy Postnatal follow‐up duration: not reported
Flow and timing	Eligible patients: 6350 Exclusions (study investigator): 24 excluded (autopsy unavailable), 1007 lost to follow‐up (15.9%) Exclusions (review team): none excluded
Comparative
Notes	Funding source: the authors declared that no funding was received for this work
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?	Yes
Could the selection of patients have introduced bias?		Low risk
Are there concerns that the included patients and setting do not match the review question?			High
DOMAIN 2: Index Test (First‐trimester scan)
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
Could the conduct or interpretation of the index test have introduced bias?		Low risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 2: Index Test (First + second‐trimester scan)
DOMAIN 2: Index Test (Single second‐trimester scan)
DOMAIN 3: Reference Standard
Is the reference standard likely to correctly classify anomalies that are externally visible, present with clinically relevant symptoms shortly after birth, or that are considered to be lethal/incompatible with life?	Yes
Is the reference standard likely to correctly classify anomalies that may present after discharge from postnatal care?	Unclear
Were the reference standard results interpreted without knowledge of the results of the index test?	No
Could the reference standard, its conduct, or its interpretation have introduced bias?		Unclear risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Did all live‐born infants receive a reference standard?	Yes
Did all live‐born infants receive the same reference standard?	No
Did all cases of fetal or perinatal loss receive the reference standard (including termination of pregnancy, intra‐uterine death, stillbirth, perinatal mortality)?	Yes
Were all patients included in the analysis?	No
Could the patient flow have introduced bias?		Unclear risk