Galindo 2011.

Study characteristics
Patient Sampling	Study design: retrospective observational study Recruitment: prenatal screening centres in Spain were invited to participate in a survey study Study start and end date: 2004 to 2006
Patient characteristics and setting	Setting: multicentre (33) (set of hospital centres which make prenatal diagnosis by ultrasound) Region(s) and country/countries from which participants were recruited: Spain Sample size: 264,612 Study eligibility criteria: the criteria for selecting the centres was that all provinces be represented (n = 50) by at least 1 centre, preferably from the public network, and/or a minimally significant activity volume set at at least 500 births/year. Centres were excluded if they did not respond to the survey or if the authors considered the response invalid. Responses were considered invalid if no data were provided, if prenatal but not postnatal data were provided, and if there was no differentiation between cases detected in the reference population and cases detected following referral from other health areas. Number of participants with the target condition: 1060 Population type: unselected population Prior testing: not reported
Index tests	Type: single‐stage screening Second‐trimester scan: Timing: second trimester of pregnancy Ultrasound scanning protocol: 68% of centres used a detailed protocol; the remaining centres did not use a standardised protocol Cardiac screening: 68% of centres used extended cardiac screening; the remaining centres did not use a standardised protocol. In 11% of centres, cardiac screening was not included in the routine second‐trimester anomaly scan, which accounted for 67% of births in the survey. Mode of examination: not reported Single or multiple operators: multiple Staff qualification and/or operator experience level: in the majority of the centres, this consisted of obstetricians with more than 5 years of experience
Target condition and reference standard(s)	Target condition(s): major cardiac anomalies Definitions used for major and minor congenital abnormalities: major or severe congenital cardiac anomalies were defined as those which have the potential to be life‐threatening and are likely to require intervention within the first year of life Reference standard (live birth): anomalies detected before birth and which were totally or partially confirmed after birth by imaging studies and surgeries were considered true positive. False‐negative cases were those diagnosed primarily after birth. This information was obtained by the collaboration of paediatricians and paediatric cardiologists from the original and referral centres. Parents were contacted when necessary. Reference standard (fetal or neonatal demise): by necropsy reports from the original and referral centre Postnatal follow‐up duration: not reported
Flow and timing	Eligible patients: 495,382 Exclusions (study investigator): 230,770 excluded (no or invalid response to survey) Exclusions (review team): none excluded
Comparative
Notes	Funding source: not reported
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?			Low concern
DOMAIN 2: Index Test (First‐trimester scan)
DOMAIN 2: Index Test (First + second‐trimester scan)
DOMAIN 2: Index Test (Single 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?			Unclear
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)?	No
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		High risk