Hartge 2011.

Study characteristics
Patient Sampling	Study design: retrospective observational study Recruitment: hospital records of 3221 pregnant women who attended the study centre for prenatal care during the study period were reviewed Study start and end date: 1993 to 2007
Patient characteristics and setting	Setting: tertiary care facility (University Hospital of Schleswig‐Holstein) Region(s) and country/countries from which participants were recruited: Luebeck, Germany Sample size: 3171 Study eligibility criteria: pregnant women with a viable singleton pregnancy, with an early anomaly scan including fetal echocardiography Number of participants with the target condition: 29 Population type: unselected population Prior testing: nuchal translucency measurement at the time of the first‐trimester scan
Index tests	Type: two‐stage screening First‐trimester scan: Timing (weeks and days gestation): 11 weeks and 0 days to 13 weeks and 6 days of gestation Ultrasound scanning protocol: detailed Cardiac screening: extended Mode of examination: primary transabdominal, transvaginal if necessary Single or multiple operators: not reported Staff qualification and/or operator experience level: not reported Second‐trimester scan: Timing (weeks and days gestation): second trimester 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 cardiac anomalies Definitions used for major and minor congenital abnormalities: isolated intracardiac shunt malformations were not classified as a major congenital cardiac defect and were excluded from the final analysis Reference standard (live birth): medical records, including reports, prints and videotapes of the ultrasound examinations, and neonatal records were evaluated Reference standard (fetal or neonatal demise): autopsy reports if available Postnatal follow‐up duration: not reported
Flow and timing	Eligible patients: 3221 Exclusions (study investigator): none reported Exclusions (review team): 50 (abnormal karyotype)
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?			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?	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