McAuliffe 2005.

Study characteristics
Patient Sampling	Study design: prospective observational study Recruitment: all pregnant women undergoing first‐trimester ultrasound screening for fetal abnormalities at the study centre were asked to participate in the study Study start and end date: July 2003 to January 2004
Patient characteristics and setting	Setting: tertiary care facility (Center of Excellence in Obstetric Ultrasound, Mount Sinai Hospital) Region(s) and country/countries from which participants were recruited: Toronto, Canada Sample size: 299 Study eligibility criteria: pregnant women with a single live fetus at 11 to 14 weeks gestation and maternal informed consent Number of participants with the target condition: 6 Population type: unselected population Prior testing: screening for chromosomal abnormalities using nuchal translucency measurement and serum biochemistry at the time of the first‐trimester scan
Index tests	Type: two‐stage screening First‐trimester scan: Timing (weeks and days gestation): 11 to 14 weeks’ gestation Ultrasound scanning protocol: basic Cardiac screening: basic Mode of examination: primary transabdominal, transvaginal if necessary Single or multiple operators: multiple (8) Staff qualification and/or operator experience level: certified in nuchal translucency scanning according to the Fetal Medicine Foundation and trained in first‐trimester anatomy screening Second‐trimester scan: Timing (weeks and days gestation): 18 to 22 weeks’ 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 was defined as lethal, incurable or curable severe abnormalities with a high risk of residual handicap. Minor was defined as other defects less severe or benign and of no functional or cosmetic significance. Reference standard (live birth): neonatal examination by a paediatrician, pregnancy outcome and postnatal findings from hospital records, chromosome analysis when indicated Reference standard (fetal or neonatal demise): autopsy Postnatal follow‐up duration: until neonatal examination
Flow and timing	Eligible patients: 325 Exclusions (study investigator): 25 lost to follow‐up (7.7%) Exclusions (review team): 1 (umbilical cord anomaly)
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?	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?	No
Could the patient flow have introduced bias?		Unclear risk