Rydberg 2017.

Study characteristics
Patient Sampling	Study design: retrospective observational study Recruitment: hospital records of fetuses screened at the study centre during the study period were reviewed Study start and end date: January 2006 to December 2013
Patient characteristics and setting	Setting: secondary care facility (Östersund County Hospital) Region(s) and country/countries from which participants were recruited: Östersund, Sweden Sample size: 10,336 Study eligibility criteria: pregnant women undergoing ultrasound screening before 22 weeks’ gestation. All babies who were delivered at the study centre, babies who delivered elsewhere as a consequence of prenatal diagnosis of fetal abnormalities detected at the study centre. Fetuses lost by miscarriages, termination of pregnancy or intrauterine fetal death with fetal abnormalities were included. Number of participants with the target condition: 166 Population type: unselected population Prior testing: in cases of increased risk for chromosomal abnormalities: amniocentesis (2006 to 2009) or combined test (> 2009)
Index tests	Type: single‐stage screening Second‐trimester scan: Timing: 18 to 22 weeks’ gestation Ultrasound scanning protocol: detailed Cardiac screening: 2006 to 2009: basic, 2010 to 2013: extended Mode of examination: transabdominal alone Single or multiple operators: multiple (9) Staff qualification and/or operator experience level: specially trained midwives (6) and obstetricians (3), experiences ranging from 1 month to 17 years
Target condition and reference standard(s)	Target condition(s): fetal structural anomalies (any type) Definitions used for major and minor congenital abnormalities: following guidelines of the Royal College of Obstetrics and Gynaecology Reference standard (live birth): neonatal examination by paediatrician, pregnancy outcome from hospital records Reference standard (fetal or neonatal demise): if available, postmortem examination Postnatal follow‐up duration: until neonatal discharge
Flow and timing	Eligible patients: 10,414 Exclusions (study investigator): none reported Exclusions (review team): 22 (21 soft markers for chromosomal abnormalities, 1 anomaly considered not detectable by prenatal ultrasound)
Comparative
Notes	Funding source: the authors have stated explicitly that there are no conflicts of interest in connection with this article. No special funding was received.
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?	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?	Yes
Could the patient flow have introduced bias?		Unclear risk