Taipale 2004.

Study characteristics
Patient Sampling	Study design: prospective observational study Recruitment: consecutive pregnant women who agreed to have 2 screening examinations by ultrasonography at the study centre Study start and end date: November 1994 to May 1996
Patient characteristics and setting	Setting: secondary care facility (Jorvi Hospital) Region(s) and country/countries from which participants were recruited: western part of greater Helsinki, Finland Sample size: 4784 Study eligibility criteria: singleton pregnancies with 2 screening examinations Number of participants with the target condition: 76 Population type: unselected population 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): 13 to 14 weeks’ gestation Ultrasound scanning protocol: detailed Cardiac screening: extended Mode of examination: transvaginal alone Single or multiple operators: multiple (6) Staff qualification and/or operator experience level: certified by the Fetal Medicine Foundation Second‐trimester scan: Timing (weeks and days gestation): 18 to 22 weeks’ gestation Ultrasound scanning protocol: detailed Cardiac screening: extended Mode of examination: transabdominal alone Single or multiple operators: multiple (5) Staff qualification and/or operator experience level: certified by the Fetal Medicine Foundation
Target condition and reference standard(s)	Target condition(s): major fetal structural abnormalities Definitions used for major and minor congenital abnormalities: not reported Reference standard (live birth): pregnancy outcome was obtained from hospital records. Obstetric and paediatric records were reviewed for all those coded with a diagnosis of malformation, including newborns referred to neonatal or paediatric units. The data were supplemented by information from the Finnish national birth and malformation registries, to which all structural and chromosomal anomalies up to 1 year of age are reported. Reference standard (fetal or neonatal demise): autopsy reports, supplemented by information from the Finnish national birth and malformation registries Postnatal follow‐up duration: 1 year after birth
Flow and timing	Eligible patients: 4856 Exclusions (study investigator): 58 excluded (3 pregnancy terminations for social reasons, 35 spontaneous abortion, 20 on gestational age of > 23 weeks' gestation at first attendance), 9 lost to follow‐up (0.19%) Exclusions (review team): 5 (4 abnormal karyotype, 1 anomaly considered minor by the review team)
Comparative
Notes	Funding source: the primary author, Pekka Taipale, received grants from the Jorvi Hospital Foundation, the Maud Kuistila Foundation and the Finnish Cultural Foundation
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)
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