Carvalho 2002.

Study characteristics
Patient Sampling	Study design: prospective observational study Recruitment: all pregnant women attending the study centre for prenatal care were offered first‐trimester screening Study start and end date: October 1995 to July 2000
Patient characteristics and setting	Setting: tertiary care facility (Clinical Hospital of São Paulo University) Region(s) and country/countries from which participants were recruited: São Paulo, Brazil Sample size: 2832 Study eligibility criteria: pregnant women receiving screening for chromosomal and fetal abnormalities by ultrasound scan between 11 and 14 weeks Number of participants with the target condition: 106 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 to 14 weeks of gestation Ultrasound scanning protocol: basic Cardiac screening: detailed early fetal echocardiography was performed in fetuses with an increased nuchal translucency thickness. It is unclear whether routine cardiac examination was performed in fetuses with normal nuchal translucency thickness. Mode of examination: primary transabdominal, transvaginal if necessary Single or multiple operators: multiple (8) Staff qualification and/or operator experience level: fetal medicine specialists (2), fetal echocardiography specialist (1), fetal medicine fellows with more than 2 years of experience (5) Second‐trimester scan: Timing: 18 weeks to 24 weeks 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): fetal structural anomalies (any type) Definitions used for major and minor congenital abnormalities: major anomalies were defined as lethal, incurable or curable severe abnormalities with high risk of residual handicap Reference standard (live birth): pregnancy outcomes from hospital records and patients themselves Reference standard (fetal or neonatal demise): pathological examination Postnatal follow‐up duration: not reported
Flow and timing	Eligible patients: 2853 Exclusions (study investigator): only the number of patients with complete follow‐up data is reported Exclusions (review team): 21 (17 soft markers for chromosomal abnormalities, 4 anomalies considered not detectable by prenatal ultrasound)
Comparative
Notes	Funding source: this project was supported by a grant acquired from FAPESP, São Paulo, Brazil (number 97/05581‐7)
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?			Unclear
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)?	Yes
Were all patients included in the analysis?	Unclear
Could the patient flow have introduced bias?		Unclear risk