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). First Jan 2004‐First April 2004 (data added to previous database from before 2003). Pregnant women. Singleton pregnancies.
Study design	Prospective cohort.
Target condition and reference standard(s)	Down's syndrome: 26 cases. Reference standards: amniocentesis, CVS and postnatal karyotyping.
Index and comparator tests	Maternal age. First trimester serum PAPP‐A (ELISA 2397, DRG International Inc). First trimester serum free ßhCG (free ßhCG IRMA K1P1001, BioSource Europe SA). Second trimester PAPP‐A and free ßhCG. First trimester NT. 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. Cases of miscarriages (n = 49) and other fetal chromosomal abnormalities excluded from the study. Unclear if other patients were 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.