Tydeman 2013.

Study characteristics
Patient Sampling	Study design: retrospective observational study Recruitment: data from prenatally diagnosed fetal anomalies were collected from the fetal medicine reporting and audit system. Those cases not diagnosed prenatally were reported by a variety of means: from paediatric departments, fetal and neonatal pathology, cytogenetic labs, the Scottish congenital heart disease register (Heartsuite) and other sources. All women had been offered a fetal anomaly scan since the early 1990s. Study start and end date: 2003 to 2009
Patient characteristics and setting	Setting: secondary care facility (Victoria Hospital) Region(s) and country/countries from which participants were recruited: Fife, United Kingdom Sample size: 25,627 Study eligibility criteria: all prenatally diagnosed fetal anomalies from the reporting and audit system and postnatally diagnosed cases in the same period Number of participants with the target condition: 125 Population type: unselected population Prior testing: dating scan, nuchal translucency measurement, maternal serum biochemistry
Index tests	Type: single‐stage screening Second‐trimester scan: Timing: 18 weeks and 0 days to 20 weeks and 6 days Ultrasound scanning protocol: detailed Cardiac screening: extended Mode of examination: not reported Single or multiple operators: multiple (2) Staff qualification and/or operator experience level: midwives specialised in fetal medicine, not further specified
Target condition and reference standard(s)	Target condition(s): 11 selected conditions: anencephaly, open spina bifida, severe heart defects, bilateral renal agenesis, lethal skeletal dysplasia, diaphragmatic hernia, exomphalos, gastroschisis, cleft lip, trisomy 18 and trisomy 13 Definitions used for major and minor congenital abnormalities: not reported Reference standard (live birth): pregnancy and neonatal outcomes were obtained from hospital records, the Scottish Congenital Heart Disease Register and other sources Reference standard (fetal or neonatal demise): data obtained from fetal and neonatal pathology departments Postnatal follow‐up duration: not reported
Flow and timing	Eligible patients: 25,644 Exclusions (study investigator): none reported Exclusions (review team): 17 (abnormal karyotype)
Comparative
Notes	Funding source: the authors declared that no funding was received for this work
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)
DOMAIN 2: Index Test (First + second‐trimester scan)
DOMAIN 2: Index Test (Single 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 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)?	Unclear
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Unclear risk