Sainz 2020.

Study characteristics
Patient Sampling	Study design: prospective observational study Recruitment: pregnant women belonging to the south of Seville, Spain were included in the study following informed consent. Recruitment methods not further specified. Study start and end date: not reported
Patient characteristics and setting	Setting: tertiary care facility (Valme’s Hospital) Region(s) and country/countries from which participants were recruited: Seville, Spain Sample size: 493 Study eligibility criteria: viable singleton pregnancy with a known pregnancy outcome Number of participants with the target condition: 13 Population type: unselected population Prior testing: not reported
Index tests	Type: two‐stage screening First‐trimester scan: Timing (weeks and days gestation): 11 to 13 weeks and 6 days of gestation Ultrasound scanning protocol: detailed Cardiac screening: extended Mode of examination: transabdominal alone Single or multiple operators: multiple (2) Staff qualification and/or operator experience level: 1 sonographer with more than 5 years of experience, 1 sonographer with standardised training but less than 1 year of experience Second‐trimester scan: Timing (weeks and days gestation): 18 to 20 weeks’ gestation Ultrasound scanning protocol: detailed Cardiac screening: extended Mode of examination: not reported Single or multiple operators: not reported Staff qualification and/or operator experience level: not reported
Target condition and reference standard(s)	Target condition(s): major fetal structural anomalies Definitions used for major and minor congenital abnormalities: European Registration of Congenital Anomalies and Twins (EUROCAT) classification system Reference standard (live birth): neonatal examination at 24 and 48 hours after delivery Reference standard (fetal or neonatal demise): pathological assessment Postnatal follow‐up duration: up to 48 hours after delivery
Flow and timing	Eligible patients: 512 Exclusions (study investigator): 2 excluded (miscarriage), 6 lost to follow‐up (1.2%) Exclusions (review team): 11 (aneuploidy)
Comparative
Notes	Funding source: no potential conflict of interest was reported by the authors. The funding source for this work was not specified.
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?	Yes
Could the selection of patients have introduced bias?		Unclear 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)
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 (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?	No
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?		High 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?	Yes
Could the patient flow have introduced bias?		Low risk