Media type: E-Article Title: Down syndrome screening using first‐trimester combined tests and contingent use of femur length at routine anomaly scan Contributor: Salomon, Laurent J.; Chevret, Sylvie; Bussieres, Laurence; Ville, Yves; Rozenberg, Patrick imprint: Wiley, 2010 Published in: Prenatal Diagnosis Language: English DOI: 10.1002/pd.2550 ISSN: 0197-3851; 1097-0223 Keywords: Genetics (clinical) ; Obstetrics and Gynecology Origination: Footnote: Description: <jats:title>Abstract</jats:title><jats:sec><jats:title>Objective</jats:title><jats:p>The objective of this study was to evaluate the performance of the contingent use of femur length (FL) at routine mid‐trimester scan in screening for Down syndrome (DS) in women having previously undergone first‐trimester screening with disclosure of risk estimates.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Data from a prospective screening trial for DS in a population of 21 492 women with 80 observed DS were used. The performance of a contingent screening strategy based on adding short FL (FL < 5th percentile) as a soft marker in women at intermediate first‐trimester risks was evaluated through simulated data.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>In our population, the median (25th–75th percentile) maternal age was 30.7 years (28.0–33.9; range: 18.0–46.3). The median (25th–75th percentile) gestational age at ultrasound examination was 12 weeks 3 days (12 weeks and 12 weeks 6 days; range: 11 weeks to 13 weeks 6 days). Contingent screening allowed an improvement in screening performance. For example, using a first‐trimester risk cut‐off of 1/100 and an intermediate‐risk population within (1/1000, 1/100) for the search of FL, a <jats:bold>sensitivity</jats:bold> (Se) of 88.4% at a 3% <jats:bold>false‐positive rate</jats:bold> (FPR) was reached. With a cut‐off of 1/200 and an intermediate‐risk population within (1/1000, 1/200), screening would allow an Se of 92.3% at a 4% FPR.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Contingent screening could be used following first‐trimester combined screening followed by second‐trimester ultrasound soft markers. This could identify indications for early invasive testing in the highest risk cases and would allow efficient and simple ultrasound‐based screening in the second trimester. This would provide an 88.4% Se for a 3% FPR, at no additional cost as compared to first‐trimester combined screening and routine mid‐trimester scan. Copyright © 2010 John Wiley & Sons, Ltd.</jats:p></jats:sec>