Muller 2003a.

Clinical features and settings	Routine screening.
Participants	5694 pregnant women who had first trimester NT and biochemical testing. France ‐ 9 centres serving 12 maternity units. January 1998‐June 2001. Singleton pregnancies. Maternal age not reported. 11‐13 weeks' gestation.
Study design	Retrospective cohort study.
Target condition and reference standard(s)	Down's syndrome: 26 cases. Reference standards: invasive testing (offered to women with high NT measurement) or follow‐up to birth.
Index and comparator tests	Maternal age. First trimester NT in 98% of patients (methods not specified. 60 sonographers ‐ 2 trained by FMF, who trained 30 in turn. 8 externally trained in France. 20 were self‐taught. Machines not specified). Frozen serum tested for: First trimester PAPP‐A (99% of patients), free ßhCG 99% of patients and AFP (93% of patients) (time‐resolved fluorescent assay, Perkin‐Elmer Life sciences). Risk cut‐point 1:250.
Follow‐up	Data from the French national screening programme used for follow‐up at birth. 211 women (3.7%) who did not return after NT or were found to be > 14 weeks were excluded. It is unclear how many patients had follow‐up to birth.
Aim of study	Prospective study of NT and retrospective evaluation of serum (in same patient population) to evaluate whether or not to move the national French Down's screening programme to a first trimester programme.
Notes	FMF methods ‐ some self‐taught sonographers.
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	Yes	Women with NT too small to measure assumed to have NT of < 0.5 mm.
Withdrawals explained? All tests	Yes	Women failing to return or who more than 14 weeks' pregnant were excluded (214).