Marchini 2010.

Clinical features and settings	Routine screening
Participants	1521 participants (18 twin and 2 triplet pregnancies; 1543 fetuses) Italy Pregnant women Singleton or multifetal pregnancies Median maternal age 31.3 years (range 18‐45 years), 19.7% ≥ 35 years 11‐14 weeks' gestation
Study design	Retrospective cohort
Target condition and reference standard(s)	Down's syndrome: 8 cases Reference standards: karyotyping or follow‐up to birth
Index and comparator tests	Maternal age First trimester NT (FMF accredited sonographers) First trimester serum free ßhCG and PAPP‐A (Kryptor analyser, Brahms) Risk cut‐point 1:300
Follow‐up	Follow‐up obtained by analysis of fetal karyotype, from patient notes and by telephoning patients
Aim of study	To evaluate the performance of the combined test compared to the NT measurement alone, in fetal aneuploidy screening in the general population and in pregnant women aged 35 years and over
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