Hernadi 1997.

Study characteristics
Patient Sampling	Study design: prospective observational study Recruitment: all pregnant women attending the department for prenatal care were offered a routine transvaginal ultrasound scan Study start and end date: 3‐year period, starting in February 1992
Patient characteristics and setting	Setting: secondary care facility (Markhot F County Hospital) Region(s) and country/countries from which participants were recruited: Eger, Hungary Sample size: 3969 Study eligibility criteria: pregnant women in the 12th week of pregnancy. Cases with missed abortion or incomplete follow‐up data were excluded. Number of participants with the target condition: 42 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): in the 12th week of gestation Ultrasound scanning protocol: basic Cardiac screening: cardiac anatomy was not examined Mode of examination: transabdominal and transvaginal Single or multiple operators: multiple (2) Staff qualification and/or operator experience level: 1 obstetrician and 1 sonographer with more than 6 years of experience Second‐trimester scan: Timing: in the 18th week of gestation Ultrasound scanning protocol: not reported Cardiac screening: not reported 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: not reported Reference standard (live birth): neonatal examination by a paediatrician Reference standard (fetal or neonatal demise): autopsy in cases of termination of pregnancy Postnatal follow‐up duration: 5 days after birth
Flow and timing	Eligible patients: 4164 Exclusions (study investigator): 139 excluded (19 spontaneous fetal death before index test, 120 fetuses on gestational age), 34 lost to follow‐up (0.8%) Exclusions (review team): 22 (soft markers for chromosomal abnormalities)
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)
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?			High
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