Audibert 2001.

Clinical features and settings	Routine screening
Participants	4130 participants France ‐ single centre May 1994 to December 1997 Pregnant women Mean maternal age 30.1 years (all under 38 years), 86% < 35, 14% ≥ 35 Singleton pregnancies 10‐14 weeks' gestation Crown‐rump length between 38 mm and 84 mm
Study design	Prospective consecutive series study
Target condition and reference standard(s)	Down's syndrome: 12 cases Reference standards: prenatal karyotyping conducted (in 7.6% of patients) depending on presence of risk > 125, high maternal age, parental anxiety, history of chromosomal defects or parental translocation or abnormal second trimester scan age Cytogenetic testing of newborns with suspected abnormalities Postmortem on terminations of pregnancy or miscarriages Follow‐up to neonatal examination in newborn
Index and comparator tests	Maternal age First trimester NT planned at 12‐13 weeks, 3 mm risk cut‐off Second trimester serum hCG between 14 and 17 weeks (Amerlite, Orthoclinical diagnostics machine), cut‐off 1:250 (Prenata software) Second trimester serum AFP between 14 and 17 weeks (Amerlite, Orthoclinical diagnostics machine), cut‐off 1:250 (Prenata software) Serum tests in 3790 women
Follow‐up	Delivery and postnatal paediatric examination 35 lost to follow‐up and excluded from analysis Pregnancy loss in 37 women due to spontaneous abortion (n = 21) or intrauterine death (n = 16) 340 women had first trimester NT but not second trimester serum testing
Aim of study	To compare first trimester NT and second trimester maternal serum measurements as alternative methods of antenatal screening in a low‐risk population and to evaluate the consequence of combining the results in the estimation of risk.
Notes	Women lost to follow‐up are excluded in the final analysis. All antenatally detected cases were terminated.
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	Yes	NT was not measured or not recorded in 219 women and these patients were excluded from the study
Withdrawals explained? All tests	Yes	340 women who did not want second trimester serum screening withdrew from that part of the study