Dane 2007.

Study characteristics
Patient Sampling	Study design: retrospective observational study Recruitment: all pregnant women attending the study centre for first‐trimester ultrasound during the study period Study start and end date: not reported
Patient characteristics and setting	Setting: tertiary care facility (Haseki Hospital) Region(s) and country/countries from which participants were recruited: Istanbul, Turkey Sample size: 1284 Study eligibility criteria: referred cases with known or suspected anomalies. Cases with minor anomalies were not included in the analyses. Isolated increased nuchal translucency was not considered an anomaly. Number of participants with the target condition: 18 Population type: unselected population Prior testing: routine nuchal translucency measurement and maternal serum biochemistry (free beta‐HCG, PAPP‐A), unclear timing
Index tests	Type: two‐stage screening First‐trimester anomaly: Timing (weeks and days gestation): 11 to 14 weeks’ gestation Ultrasound scanning protocol: basic Cardiac screening: not reported Mode of examination: primary transabdominal, transvaginal if necessary Single or multiple operators: multiple (2) Staff qualification and/or operator experience level: 6 and 2 years of experience in ultrasound screening Second‐trimester anomaly: Timing: 22 to 24 weeks’ gestation Ultrasound scanning protocol: not reported Cardiac screening: not reported Mode of examination: not reported Single or multiple operators: multiple (2) Staff qualification and/or operator experience level: 6 and 2 years of experience in ultrasound screening
Target condition and reference standard(s)	Target condition(s): major fetal structural anomalies Definitions used for major and minor congenital abnormalities: minor anomalies: mild hydronephrosis, choroid plexus cysts, mild ventriculomegaly, digital anomalies and cardiac defects not requiring treatment Reference standard (live birth): pregnancy outcomes were obtained from the hospital records and from the patients themselves Reference standard (fetal or neonatal demise): not reported Postnatal follow‐up duration: not reported
Flow and timing	Eligible patients: 1326 Exclusions (study investigator): 36 lost to follow‐up (2.7%) Exclusions (review team): 6 (2 soft markers for chromosomal abnormalities, 4 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?			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?			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