Natu 2014.

Study characteristics
Patient Sampling	Study design: prospective observational study Recruitment: pregnant women attending the facility for prenatal care were informed and enrolled after informed consent Study start and end date: December 2011 to October 2013
Patient characteristics and setting	Setting: tertiary care facility (Sri Aurobindo Institute of Medical Sciences) Region(s) and country/countries from which participants were recruited: Indore, India Sample size: 548 Study eligibility criteria: pregnant women with a viable pregnancy before 14 weeks’ gestation were included. Missed abortions and molar pregnancies were excluded. Patients were divided into two groups based on risk of having a fetus affected by a congenital anomaly. High‐risk pregnancy was defined as any one of the following risk factors: maternal age > 30 years, previous history of any congenital anomaly or pregnancy loss, family history of structural defects, pregnancy after assisted reproductive techniques, maternal diseases like diabetes mellitus or epilepsy, multiple pregnancy, history of smoking or alcohol consumption in the antenatal period, previous affected child with chromosomal aberration. Number of participants with the target condition: 3 Population type (cohort included for meta‐analysis): low‐risk Prior testing: not reported
Index tests	Type: two‐stage screening First‐trimester scan: Timing (weeks and days gestation): 11 to 14 weeks’ gestation Ultrasound scanning protocol: basic Cardiac screening: basic Mode of examination: not reported Single or multiple operators: not reported Staff qualification and/or operator experience level: not reported Second‐trimester scan: Timing: 18 to 22 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
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): neonatal examination by a paediatrician Reference standard (fetal or neonatal demise): not reported Postnatal follow‐up duration: until neonatal examination
Flow and timing	Eligible patients: 1500 Exclusions (study investigator): 323 excluded (321 on exclusion criteria, 2 unspecified exclusions), 130 lost to follow‐up (11.0%) Exclusions (review team): 499 (496 high‐risk pregnancies, 3 soft markers for chromosomal abnormalities from the low‐risk cohort)
Comparative
Notes	Funding source: not reported
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?	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?	No
Could the patient flow have introduced bias?		Unclear risk