Gyselaers 2005.

Clinical features and settings	Routine screening
Participants	13,267 participants (13,207 participant received both NT test and serum testing) Belgium ‐ multicentre study (35 centres) Data from January 2004‐April 2004 added to previous database from before 2003 Pregnant women First and second trimester testing
Study design	Prospective cohort
Target condition and reference standard(s)	Down's syndrome: 26 cases Reference standards: CVS, amniocentesis or follow‐up to birth
Index and comparator tests	Maternal age First trimester NT (FMF methods) First trimester PAPP‐A (ELISA 2397, DRG International Inc) and free ßhCG (IRMA K1P1001) Second trimester PAPP‐A and free ßhCG Risk cut‐points of 1:200 and 1:300
Follow‐up	Follow‐up to birth reported by mail by obstetricians. Non‐responding obstetricians contacted personally to obtain missing data. Results of follow‐up reported by mail by obstetricians. Non‐responding obstetricians contacted personally to obtain missing data Cases of miscarriages (n = 49) and other fetal chromosomal abnormalities excluded from the study. Unclear if other patients lost to follow‐up
Aim of study	To evaluate the performance of a first trimester fetal aneuploidy screening programme
Notes	Women with miscarriages or cases of other chromosomal defects were excluded from the study. 9 live births of babies with Down's syndrome
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	Yes	Numbers of women excluded due to miscarriage or other chromosomal defects and numbers not undergoing NT and biochemical testing reported.