Liao 2021.

Study characteristics
Patient Sampling	Study design: retrospective observational study Recruitment: data from all pregnant women that attended the study centre for a routine first‐trimester scan were evaluated Study start and end date: October 2008 to December 2015
Patient characteristics and setting	Setting: tertiary care facility (Shenzhen Maternity & Child Healthcare Hospital) Region(s) and country/countries from which participants were recruited: Shenzhen, China Sample size: 53,213 Study eligibility criteria: singleton pregnancies with a live fetus between 11 and 13 + 6 weeks and complete follow‐up data were included. Unexplained miscarriages and fetal deaths were excluded. Number of participants with the target condition: 1920 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): 11 to 13 weeks and 6 days of gestation Ultrasound scanning protocol: detailed Cardiac screening: extended Mode of examination: primary transabdominal, transvaginal if necessary Single or multiple operators: multiple Staff qualification and/or operator experience level: all sonographers underwent a rigorous 6‐month training Second‐trimester scan: Timing: 18 to 24 weeks’ gestation Ultrasound scanning protocol: not reported Cardiac screening: extended Mode of examination: not reported Single or multiple operators: multiple Staff qualification and/or operator experience level: all sonographers underwent a rigorous 6 months' training
Target condition and reference standard(s)	Target condition(s): fetal structural anomalies (any type) Definitions used for major and minor congenital abnormalities: cardiac anomalies considered minor: rhabdomyoma, ventricular septal defects, persistent left superior vena cava and vascular rings. No further definitions for major and minor congenital anomalies given. Reference standard (live birth): data on postnatal findings were obtained from Shenzhen Birth Defects Surveillance Database and Chinese Birth Defects Monitoring Network. In addition, data from hospital records and telephone calls to patients themselves were collected. Reference standard (fetal or neonatal demise): results of genetic tests and autopsies were extracted from medical records if available Postnatal follow‐up duration: not reported
Flow and timing	Eligible patients: 59063 Exclusions (study investigator): 420 excluded (miscarriage or spontaneous fetal death), 5294 lost to follow‐up (9.0%) Exclusions (review team): 136 (105 anomalies associated with holoprosencephaly that were reported separately in addition to the main diagnosis, 19 anomalies considered not detectable by prenatal ultrasound, 12 physiological midgut herniations)
Comparative
Notes	Funding source: the study was supported by the National Key Research and Development Program of China (2018YFC1002202), the National Nature Science Foundation of China (81771598,81571758) and the Shenzhen Science and Technology project (JCYJ20170307091013214)
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?			High
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?	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)?	Yes
Were all patients included in the analysis?	No
Could the patient flow have introduced bias?		Unclear risk