{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,9,3]],"date-time":"2024-09-03T20:20:55Z","timestamp":1725394855126},"reference-count":12,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2006,6,1]],"date-time":"2006-06-01T00:00:00Z","timestamp":1149120000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Mr Gopal Savjani","award":["DSL Laboratories Inc.,"],"award-info":[{"award-number":["DSL Laboratories Inc.,"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Prenatal Diagnosis"],"published-print":{"date-parts":[[2006,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To examine the performance of Integrated Down syndrome screening (first\u2010 and second\u2010trimester measurements integrated into a single screening test) when ratios of the levels of the same serum markers measured in both these trimesters (cross\u2010trimester ratios) are added as new screening markers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using data from Serum Urine and Ultrasound Screening Study (SURUSS), second\u2010trimester concentrations (in multiples of the median, or MoM) of pregnancy associated plasma protein A (PAPP\u2010A), alphafetoprotein (AFP), unconjugated oestriol (uE<jats:sub>3<\/jats:sub>), human chorionic gonadotrophin (hCG) (free \u03b2 and total), and inhibin\u2010A were divided by the first\u2010trimester concentration to obtain a cross\u2010trimester (CT) ratio for each analyte in 74 Down syndrome and 492 unaffected pregnancies. We identified CT ratios that improved screening performance and then, using Monte Carlo simulations, estimated the efficacy and cost effectiveness of adding them to the Integrated and serum Integrated tests.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>All the median CT ratios differed significantly between Down syndrome and unaffected pregnancies. Setting the Integrated test to achieve a 90% detection rate, the false\u2010positive rate (FPR) was 0.7% with CT ratios for PAPP\u2010A, uE<jats:sub>3<\/jats:sub>, inhibin\u2010A, and total hCG compared with 2.2% without CT ratios, a reduction of about two\u2010thirds. Using the serum Integrated test to achieve the same 90% detection rate and the first\u2010trimester measurements made at 11 completed weeks of pregnancy, the corresponding FPRs were 2.4 and 8.1%, a similar proportional reduction. The AFP CT ratio had little effect on screening performance. Using CT ratios did not increase the cost per Down syndrome pregnancy detected.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The addition of CT ratios to an Integrated test substantially improves the efficacy and safety of prenatal screening for Down syndrome. It is cost effective and could be usefully introduced into screening programmes. 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