Cuckle 2008.

Clinical features and settings	Routine screening
Participants	36,740 participants undergoing first trimester screening (32,355 also underwent second trimester screening) USA ‐ 15 centres, FASTER trial Pregnant women Singleton pregnancies Maternal age not reported 11‐13 and 15‐18 weeks' gestation
Study design	Prospective cohort
Target condition and reference standard(s)	Down's syndrome: 116 cases (86 cases had both first trimester and second trimester screening) Reference standards: karyotyping or follow‐up to birth
Index and comparator tests	Maternal age First trimester NT, PAPP‐A and free ßhCG (details not reported) Second trimester AFP, total hCG, uE3 and inhibin‐A (details not reported)
Follow‐up	Details of follow‐up not reported
Aim of study	To compare the contingent, step‐wise and integrated screening policies
Test characteristics
Reference standard used
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