Hautala 2019.

Study characteristics
Patient Sampling	Study design: population‐based retrospective cohort study Recruitment: study data were collected from national registers containing information on all births, stillbirths and pregnancy terminations due to fetal anomaly, including all prenatally and postnatally diagnosed cases of univentricular heart and transposition of the great arteries Study start and end date: 2004 to 2014
Patient characteristics and setting	Setting: multiple population‐based national registers: 1) the National Register of Paediatric Cardiac Surgery; (2) the Finnish Register of Congenital Malformations; (3) the Register of Induced Abortions; (4) the Medical Birth Register; and (5) the Cause‐of‐Death Register Region(s) and country/countries from which participants were recruited: Finland Sample size: 299,559 Study eligibility criteria: cases with univentricular heart and transposition of great arteries Number of participants with the target condition: 232 Population type: unselected population Prior testing: nuchal translucency measurement, maternal serum biochemistry
Index tests	Type: single‐stage screening Second‐trimester scan: Timing (weeks and days gestation): 18 weeks and 0 days to 21 weeks and 6 days of gestation Ultrasound scanning protocol: 2004 to 2009: no standardised national screening programme, 2010 to 2014: detailed Cardiac screening: 2004 to 2009: no standardised national screening programme, 2010 to 2014: extended Mode of examination: not reported Single or multiple operators: multiple Staff qualification and/or operator experience level: examinations are mainly performed by trained midwives, not further specified
Target condition and reference standard(s)	Target condition(s): selected cardiac anomalies; univentricular heart and transposition of the great arteries Definitions used for major and minor congenital abnormalities: not reported Reference standard (live birth): data were cross‐checked with the mothers’ and live‐born infants’ identification numbers and all information was verified from hospital records, including prenatal and postnatal reports, karyotype. One paediatric and fetal cardiologist confirmed all cardiac diagnoses and one clinical geneticist confirmed all extra‐cardiac malformations. Reference standard (fetal or neonatal demise): data were verified using autopsy reports Postnatal follow‐up duration: not reported
Flow and timing	Eligible patients: 651,969 Exclusions (study investigator): none reported Exclusions (review team): 352,410 (352,332 cases born during the pre‐screening period (2004 to 2009), 78 cases of a selected anomaly within the larger category of conotruncal anomalies)
Comparative
Notes	Funding source: all authors declare no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous 3 years; no other relationships or activities that could appear to have influenced the submitted 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?	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)?	No
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		High risk