Boyd 2011.

Study characteristics
Patient Sampling	Study design: population‐based retrospective cohort study based on data from the British Isles Network of Congenital Anomaly Registers (BINOCAR) database Recruitment: BINOCAR is a network of regional and disease‐specific population‐based registers across the British Isles. All births in Wales and 43% of births in England are covered by the regional congenital anomaly registers. Cases included all fetuses and infants with the target condition of interest notified within 1 year with a date of delivery/termination during the study period. Study start and end date: January 2005 to December 2006
Patient characteristics and setting	Setting: congenital anomaly registry Region(s) and country/countries from which participants were recruited: United Kingdom (South Central, East Midlands & South Yorkshire, South West, North East & North Cumbria, West Midlands and Wales) Sample size: 601,500 Study eligibility criteria: cases included all affected fetuses and infants with 1 of the 9 major structural anomaly groups selected in discussion with the Fetal Anomaly Screening Programme (FASP), notified within 1 year with a date of delivery/termination Number of participants with the target condition: 2839 Population type: unselected population Prior testing: not reported
Index tests	Type: single‐stage screening Second‐trimester scan: Timing (weeks and days gestation): 18 weeks and 0 days to 20 weeks and 6 days of pregnancy 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): 9 selected major anomaly groups: anencephaly, spina bifida, serious cardiac anomalies, diaphragmatic hernia, gastroschisis, exomphalos, bilateral renal agenesis, lethal/severe skeletal dysplasias, cleft lip with or without palate Definitions used for major and minor congenital abnormalities: not reported Reference standard (live birth): to achieve high levels of ascertainment and completeness, BINOCAR registers identify cases using multiple source notifications prospectively throughout pregnancy and confirmation or otherwise at delivery. These sources include laboratories, parents, ultrasound departments, delivery suites, obstetric notes, neonatal units, child health systems, inpatient administration systems and paediatric notes. Reference standard (fetal or neonatal demise): post‐mortem reports Postnatal follow‐up duration: anomalies are included in the registry when diagnosed up to the age of 5 years
Flow and timing	Eligible patients: 601,545 Exclusions (study investigator): none reported Exclusions (review team): 45 (unknown gestation at time of prenatal diagnosis)
Comparative
Notes	Funding source: this paper reports on an independent study which is funded/part‐funded by the Policy Research Programme in the Department of Health and the Healthcare Quality Improvement Partnership (HQIP). Part funding is also from local primary care trusts and the Welsh Assembly Government.
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?	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