Michailidis 2001.

Clinical features and settings	Routine screening
Participants	7447 participants UK ‐ hospital maternity unit January 1995 to January 2000 Pregnant women Mean age 30.1 years (13‐50 years), 21.1% ≥ 35 years, 11.9% ≥ 37 years 10‐14 weeks' gestation
Study design	Prospective cohort study
Target condition and reference standard(s)	Down’s syndrome: 23 cases Reference standards: karyotyping in women considered at risk due to index test results, age or family history or those with considerable anxiety (632 women, 8.5%). Follow‐up to birth
Index and comparator tests	Maternal age First trimester NT in all patients (fetus in mid‐sagittal section. Maximum thickness of subcutaneous translucency between skin and soft tissue overlying the C‐spine with the fetus in the ventral position) Second trimester AFP, free ßhCG in 65% of patients with NT (radio‐immunoassay and immunoradiometric assays)
Follow‐up	Outcome at birth assess from hospital database, labour ward records or directly from patients. Follow‐up data in 7447 patients (87% of initial patient cohort). Patients without follow‐up excluded
Aim of study	To asses the effectiveness of antenatal screening for trisomy 21 by first trimester sonography followed by second trimester biochemical screening
Notes	2nd trimester data not analysed 4 live births: 1 diagnosed before birth and chose not to abort. 3 diagnosed after birth (no invasive testing was conducted)
Table of Methodological Quality
Item	Authors' judgement	Description
Representative spectrum? All tests	Yes	Routine screening of typical pregnant population
Acceptable reference standard? All tests	Yes	Karyotyping or follow‐up to birth
Partial verification avoided? All tests	Yes	All women received a reference standard
Differential verification avoided? All tests	No	Choice of reference standard depended on index test results
Incorporation avoided? All tests	Yes	Reference standard was independent of the index test
Reference standard results blinded? All tests	No	Reference standard interpreted with knowledge of index test results
Index test results blinded? All tests	Yes	Index test interpreted without knowledge of reference standard results
Relevant clinical information? All tests	Yes	Information available as would be in standard clinical practice
Uninterpretable results reported? All tests	No	No details given for test failures/uninterpretable measurements
Withdrawals explained? All tests	No	No details of withdrawals given