Vadiveloo 2009.

Clinical features and settings	Routine screening
Participants	10,189 participants UK ‐ screening programme July 2000 ‐ October 2005 Pregnant women Median maternal age 33.1 years, 36.9% ≥ 35 years 9‐14 weeks' gestation
Study design	Retrospective cohort
Target condition and reference standard(s)	Down's syndrome: 44 cases Reference standards: karyotyping or follow‐up to birth
Index and comparator tests	Maternal age First trimester NT (trained sonographers) First trimester PAPP‐A and free ßhCG (DELFIA fluoroimmunoassay, PerkinElmer LAS) Contingent: biochemistry high risk cut‐off 1:42, low risk cut‐off 1:1000. If biochemical/maternal age risk between 1:42 and 1:1000, NT results added and combined risk calculated. Final cut‐point 1:250
Follow‐up	Not reported
Aim of study	To assess the performance of a 2‐stage screening protocol for Down's syndrome based on initial serum marker analysis for all women and NT measurement only in women with intermediate risks
Notes
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	Unclear	Unclear if 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