Gu 2011.

Study characteristics
Patient Sampling	Study design: retrospective observational study Recruitment: hospital records of 2844 pregnant women who received ultrasound screening at the facility during the study period were reviewed Study start and end date: February 2007 to July 2010
Patient characteristics and setting	Setting: tertiary care facility (Nanjing Drum Tower Hospital) Region(s) and country/countries from which participants were recruited: Nanjing, China Sample size: 3008 Study eligibility criteria: data were collected from pregnant women who had ultrasound screening during the first and second trimester in the study centre Number of participants with the target condition: 98 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: basic Cardiac screening: basic Mode of examination: primary transabdominal, transvaginal if necessary Single or multiple operators: not reported Staff qualification and/or operator experience level: not reported Second‐trimester scan: Type: single‐stage screening (index test 3) Timing: 18 to 24 weeks’ gestation 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 Second‐trimester anomaly scan: Timing (weeks and days gestation): 18 to 24 weeks of gestation 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): fetal structural anomalies (any type) Definitions used for major and minor congenital abnormalities: not reported Reference standard (live birth): follow‐up visits were performed for all newborns Reference standard (fetal or neonatal demise): not reported Postnatal follow‐up duration: not reported
Flow and timing	Eligible patients: 3135 Exclusions (study investigator): none reported Exclusions (review team): 127 (75 fetal death before index test, 32 soft markers for chromosomal abnormalities, 14 unspecified umbilical cord abnormalities, 5 fetal growth abnormalities, 1 anomaly considered not detectable by prenatal ultrasound)
Comparative
Notes	Funding source: National Project of Scientific and Technical Supporting Programs of China during the 11th Five‐year Plan Period (Grant No 2006BAl05A04)
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Unclear
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
Could the selection of patients have introduced bias?		Unclear 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)?	Unclear
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Unclear risk