Johnson 1997.

Study characteristics
Patient Sampling	Study design: retrospective observational study Recruitment: hospital records of pregnant women who underwent ultrasound screening as part of routine antenatal care or on self‐referral were reviewed Study start and end date: September 1992 to January 1996
Patient characteristics and setting	Setting: multicentre (8) (7 secondary care facilities; 1 tertiary care facility) Region(s) and country/countries from which participants were recruited: Basildon, Ascot, London, Camberley, Haywards Heath, Sidcup and Chertsey, United Kingdom Sample size: 55,237 Study eligibility criteria: pregnant women with live fetuses at 10 to 14 weeks’ gestation Number of participants with the target condition: 47 Population type: mixed population of unselected women screened as part of routine prenatal at one of the 7 secondary care facilities (n = 28,891) and unselected self‐referred women screened at the tertiary care facility (n = 26,346) 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): 10 to 14 weeks’ gestation Ultrasound scanning protocol: basic Cardiac screening: not reported Mode of examination: not reported Single or multiple operators: multiple Staff qualification and/or operator experience level: (obstetric) sonographer, not further specified Second‐trimester scan: Timing: 18 to 22 weeks’ gestation Ultrasound scanning protocol: examination is described as detailed, protocol not reported Cardiac screening: not reported Mode of examination: not reported Single or multiple operators: multiple Staff qualification and/or operator experience level: (obstetric) sonographer, not further specified
Target condition and reference standard(s)	Target condition(s): anencephaly Definitions used for major and minor congenital abnormalities: not applicable Reference standard (live birth): pregnancy outcomes from hospital records or patients themselves Reference standard (fetal or neonatal demise): not reported Postnatal follow‐up duration: not reported
Flow and timing	Eligible patients: 55,237 Exclusions (study investigator): none reported 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?			Unclear
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?	Yes
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?		Low 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