Kuc 2010.

Clinical features and settings	Routine screening
Participants	27,291 participants: 223 cases and 22,157 controls (not matched) The Netherlands ‐ The Dutch National Institute for Public Health and the Environment Dates not specified Pregnant women Maternal age not reported 8‐13 weeks' gestation
Study design	Case‐control study
Target condition and reference standard(s)	Down's syndrome: 223 cases Reference standards: karyotyping or follow‐up to birth
Index and comparator tests	Maternal age First trimester NT (FMF trained sonographers) First trimester free ßhCG and PAPP‐A (automated dissociation‐enhanced lanthanide fluorescent immunoassay, AutoDELFIA, PerkinElmer)
Follow‐up	Known outcomes for cases and controls
Aim of study	To estimate the effect of timing of serum collection on screening performance
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	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