Hafner 2003.

Study characteristics
Patient Sampling	Study design: retrospective observational study Recruitment: hospital records of all pregnant women who booked for delivery at the hospital in the first trimester of pregnancy during the study period were reviewed Study start and end date: January 1994 to December 2000
Patient characteristics and setting	Setting: tertiary care facility (Donauspital) Region(s) and country/countries from which participants were recruited: Vienna, Austria Sample size: 12,978 Study eligibility criteria: pregnant women with a viable fetus and who had a nuchal translucency measurement performed at the study centre. Criteria for exclusion were aneuploidy and cases who were scanned at the study centre following referral for increased fetal nuchal translucency. Number of participants with the target condition: 27 Population type: unselected population Prior testing: nuchal translucency measurement at the time of the first‐trimester scan
Index tests	Type: single‐stage screening Second‐trimester scan: Timing (weeks and days gestation): 22 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 cardiac anomalies Definitions used for major and minor congenital abnormalities: all cardiac anomalies were defined as major, except for small muscular ventricular septal defects (VSDs), atrial septal defects II (ASDII) and patent ductus arteriosus Reference standard (live birth): neonatal examination by an experienced paediatrician. Echocardiography was performed when there was a suspect finding in the prenatal scanning or when a cardiac murmur or other irregularity was observed. When CHD was detected after the newborn was discharged, the department that made the diagnosis informed the study centre. Reference standard (fetal or neonatal demise): not reported Postnatal follow‐up duration: until neonatal examination
Flow and timing	Eligible patients: 13,716 Exclusions (study investigator): 117 (89 aneuploidy, 28 spontaneous fetal death before index test), 621 lost to follow‐up (45%) 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?			Low concern
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)?	Unclear
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Unclear risk