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112.568 170.811 l S EMC Q q 0 18 612 756 re W* n /Artifact <>BDC Q 0 0.447 0.659 rg 131.983 285.352 463.097 15.66 re f 131.092 301.903 m 595.97 301.903 l 595.079 301.012 l 131.983 301.012 l h f 131.092 301.903 m 131.092 284.462 l 131.983 285.352 l 131.983 301.012 l h f 595.97 301.903 m 595.97 284.462 l 595.079 285.352 l 595.079 301.012 l h f 131.092 284.462 m 595.97 284.462 l 595.079 285.352 l 131.983 285.352 l h f EMC EMC EMC /Article <>BDC q 0 18 612 756 re W* n q 103.3061676 0 0 53.4342194 7.1245575 714.8661194 cm /Im0 Do Q q 341.9790497 0 0 40.6100159 110.4307404 727.6903381 cm /Im1 Do Q 1 1 1 rg BT /TT0 1 Tf 7.9795 0 0 7.9795 117.1991 694.8566 Tm ( Note: )Tj 0 0 0 rg /TT1 1 Tf ( Performing your original search, )Tj /TT0 1 Tf (combined and quadruple test)Tj /TT1 1 Tf (, in PubMed Central will retrieve )Tj ET 0 0.314 0.627 RG 0.383 w 10 M 0 j 0 J []0 d 485.677 693.708 m 534.017 693.708 l S 0 0.314 0.627 rg BT /TT0 1 Tf 7.9795 0 0 7.9795 485.6769 694.8566 Tm (439 citations)Tj 0 0 0 rg /TT1 1 Tf (.)Tj 0 0.333 0.667 rg /TT2 1 Tf -46.491 -2.38 Td (Journal List)Tj 0 0 0 rg ( > )Tj 0 0.333 0.667 rg (BMJ)Tj 0 0 0 rg ( > )Tj 0 0.333 0.667 rg (v.323\(7310\); Aug 25, 2001)Tj 0 0.251 0.502 rg /TT1 1 Tf 7.4808 0 0 7.4808 12.8242 656.9377 Tm (Abstract)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 40.2638 656.9377 Tm ( )Tj ET q 3.5622864 0 0 7.1245575 12.8242188 641.7085419 cm /Im2 Do Q 0.502 0.502 0.502 rg BT /TT1 1 Tf 7.4808 0 0 7.4808 16.3865 643.401 Tm (Full Text)Tj 0 0 1 rg /T1_0 1 Tf 9.9744 0 0 9.9744 45.0679 643.401 Tm ( )Tj 0 0.251 0.502 rg /TT1 1 Tf 7.4808 0 0 7.4808 19.9488 629.8643 Tm (Figures and Tables)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 83.9769 629.8643 Tm ( )Tj /TT1 1 Tf 7.4808 0 0 7.4808 12.8242 616.3277 Tm (PDF \(268K\))Tj /T1_0 1 Tf 9.9744 0 0 9.9744 52.3153 616.3277 Tm ( )Tj /TT1 1 Tf 7.4808 0 0 7.4808 12.8242 602.791 Tm (Contents)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 42.7623 602.791 Tm ( )Tj /TT1 1 Tf 7.4808 0 0 7.4808 12.8242 589.2543 Tm (Archive)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 37.7652 589.2543 Tm ( )Tj 0 0 0 rg /TT0 1 Tf 7.4808 0 0 7.4808 9.2619 563.551 Tm (Related material:)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 95.9308 547.9493 Tm ( )Tj /TT0 1 Tf 7.4808 0 0 7.4808 9.2619 515.4082 Tm (PubMed articles by:)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 79.933 515.4082 Tm ( )Tj 0 0.251 0.502 rg /TT1 1 Tf 7.4808 0 0 7.4808 12.8242 504.6858 Tm (Gilbert, R.)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 46.4953 504.6858 Tm ( )Tj /TT1 1 Tf 7.4808 0 0 7.4808 12.8242 491.1491 Tm (Augood, C.)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 50.2506 491.1491 Tm ( )Tj /TT1 1 Tf 7.4808 0 0 7.4808 12.8242 477.6124 Tm (Gupta, R.)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 44.842 477.6124 Tm ( )Tj /TT1 1 Tf 7.4808 0 0 7.4808 12.8242 464.0758 Tm (van der Meulen, J.)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 74.3612 464.0758 Tm ( )Tj 0 0 0 rg 8.4782 0 0 8.4782 131.092 657.2253 Tm (BMJ. 2001 August 25; 323\(7310\): 423. )Tj ET 0.427 w 131.092 639.536 m 165.48 639.536 l S 0 0.314 0.627 rg BT /T1_0 1 Tf 8.4782 0 0 8.4782 131.092 640.8174 Tm (Copyright)Tj 0 0 0 rg ( \251 2001, BMJ)Tj /T1_1 1 Tf 12.468 0 0 12.468 131.092 612.2552 Tm (Screening for Down's syndrome: effects, safety, and cost effectiveness o\ f first and )Tj 0 -1.2 TD (second trimester strategies)Tj /T1_0 1 Tf 10.9718 0 0 10.9718 131.092 566.1281 Tm (R E Gilbert, )Tj /T1_2 1 Tf (senior lecturer in clinical epidemiology)Tj /T1_0 1 Tf (,)Tj /T1_2 1 Tf 8.7775 0 0 8.7775 363.6179 571.7457 Tm (a)Tj /T1_0 1 Tf 10.9718 0 0 10.9718 368.0066 566.1281 Tm ( C Augood, )Tj /T1_2 1 Tf (research fellow in systematic reviews)Tj /T1_0 1 Tf (,)Tj /T1_2 1 Tf 8.7775 0 0 8.7775 131.092 554.6272 Tm (a)Tj /T1_0 1 Tf 10.9718 0 0 10.9718 135.4807 549.0096 Tm ( R Gupta, )Tj /T1_2 1 Tf (research assistant in statistics)Tj /T1_0 1 Tf (,)Tj /T1_2 1 Tf 8.7775 0 0 8.7775 315.309 554.6272 Tm (a)Tj /T1_0 1 Tf 10.9718 0 0 10.9718 319.6977 549.0096 Tm ( A E Ades, )Tj /T1_2 1 Tf (reader in biostatistics)Tj /T1_0 1 Tf (,)Tj /T1_2 1 Tf 8.7775 0 0 8.7775 469.0352 554.6272 Tm (b)Tj /T1_0 1 Tf 10.9718 0 0 10.9718 473.424 549.0096 Tm ( S Logan, )Tj /T1_2 1 Tf (senior lecturer )Tj -31.201 -1.56 Td (in epidemiology)Tj /T1_0 1 Tf (,)Tj /T1_2 1 Tf 8.7775 0 0 8.7775 204.2302 537.5087 Tm (a)Tj /T1_0 1 Tf 10.9718 0 0 10.9718 208.6189 531.8911 Tm ( M Sculpher, )Tj /T1_2 1 Tf (senior research fellow)Tj /T1_0 1 Tf (,)Tj /T1_2 1 Tf 8.7775 0 0 8.7775 369.2245 537.5087 Tm (c)Tj /T1_0 1 Tf 10.9718 0 0 10.9718 373.1217 531.8911 Tm ( and J H P van der Meulen, )Tj /T1_2 1 Tf (senior lecturer in )Tj -22.059 -1.56 Td (clinical epidemiology)Tj 8.7775 0 0 8.7775 225.8666 520.3902 Tm (d)Tj 6.7826 0 0 6.7826 131.092 491.4983 Tm (a)Tj /T1_0 1 Tf 8.4782 0 0 8.4782 134.4833 487.1574 Tm (Systematic Reviews Training Unit, Department of Paediatric Epidemiology \ and Biostatistics, Institute of Child Health, London )Tj -0.4 -1.56 Td (WC1N 1EH, )Tj /T1_2 1 Tf 6.7826 0 0 6.7826 177.0101 478.2704 Tm (b)Tj /T1_0 1 Tf 8.4782 0 0 8.4782 180.4014 473.9295 Tm (Department of Paediatric Epidemiology and Biostatistics, Institute of Ch\ ild Health, )Tj /T1_2 1 Tf 6.7826 0 0 6.7826 464.8799 478.2704 Tm (c)Tj /T1_0 1 Tf 8.4782 0 0 8.4782 467.8914 473.9295 Tm (Centre for Health Economics, )Tj -39.725 -1.56 Td (University of York, Heslington, York YO1 5DD, )Tj /T1_2 1 Tf 6.7826 0 0 6.7826 300.1648 465.0424 Tm (d)Tj /T1_0 1 Tf 8.4782 0 0 8.4782 303.5561 460.7016 Tm (Health Services Research Unit, Department of Public Health and Policy, L\ ondon )Tj -20.342 -1.2 Td (School of Hygiene and Tropical Medicine, London WC1E 7HT)Tj 0 -2.797 TD (Contributors: REG, AEA, SL, MS, and JHPvdM contributed to the study desi\ gn. CA reviewed the literature. RG did the computer )Tj 0 -1.2 TD (programming, which was supervised by AEA. MS advised on the economic ana\ lysis. JHPvdM devised the analytical strategy for the )Tj T* (screening tests. All authors contributed to writing the manuscript. REG \ wrote the final version, and acts as guarantor for the s)Tj (tudy.)Tj 0 -2.797 TD (Correspondence to: R E Gilbert )Tj ET 240.588 381.477 m 318.563 381.477 l S 0 0.314 0.627 rg BT /T1_0 1 Tf 8.4782 0 0 8.4782 240.5883 382.7589 Tm (r.gilbert@ich.ucl.ac.uk)Tj 0 0 0 rg ( )Tj -12.915 -2.965 Td (Accepted May 21, 2001.)Tj ET q 2.849823 0 0 5.699646 142.491272 329.1185913 cm /Im3 Do Q BT /T1_0 1 Tf 8.4782 0 0 8.4782 145.3411 330.4859 Tm ( This article has been )Tj ET 219.509 329.204 m 246.588 329.204 l S 0 0.314 0.627 rg BT /T1_0 1 Tf 8.4782 0 0 8.4782 219.5087 330.4859 Tm (cited by)Tj 0 0 0 rg ( other articles in PMC.)Tj 0 0.251 0.502 rg /TT1 1 Tf 7.4808 0 0 7.4808 22.0862 293.6208 Tm (Top)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 34.9756 293.6208 Tm ( )Tj ET q 3.5622864 0 0 7.1245575 14.9615784 278.3916931 cm /Im2 Do Q 0.502 0.502 0.502 rg BT /TT1 1 Tf 7.4808 0 0 7.4808 18.5239 280.0842 Tm (Abstract)Tj 0 0 1 rg /T1_0 1 Tf 9.9744 0 0 9.9744 45.9634 280.0842 Tm ( )Tj 0 0.251 0.502 rg /TT1 1 Tf 7.4808 0 0 7.4808 22.0862 266.5475 Tm (Introduction)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 61.1733 266.5475 Tm ( )Tj /TT1 1 Tf 7.4808 0 0 7.4808 22.0862 253.0108 Tm (Methods)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 50.775 253.0108 Tm ( )Tj /TT1 1 Tf 7.4808 0 0 7.4808 22.0862 239.4742 Tm (Results)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 47.0271 239.4742 Tm ( )Tj /TT1 1 Tf 7.4808 0 0 7.4808 22.0862 225.9375 Tm (Discussion)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 58.2483 225.9375 Tm ( )Tj /TT1 1 Tf 7.4808 0 0 7.4808 22.0862 214.3161 Tm (Commentary: Results may )Tj 0 -1.447 TD (not be widely applicable)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 101.5022 203.4951 Tm ( )Tj /TT1 1 Tf 7.4808 0 0 7.4808 22.0862 189.9585 Tm (Authors' response)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 82.1419 189.9585 Tm ( )Tj /TT1 1 Tf 7.4808 0 0 7.4808 22.0862 176.4218 Tm (References)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 60.3354 176.4218 Tm ( )Tj 1 1 1 rg /TT3 1 Tf 10.9718 0 0 10.9718 337.566 289.5856 Tm (Abstract)Tj 0 0 0 rg /T1_1 1 Tf 9.9744 0 0 9.9744 131.092 262.3583 Tm (Objective)Tj /T1_0 1 Tf 0 -1.2 TD (To compare the effects, safety, and cost effectiveness of antenatal scre\ ening strategies for Down's syndrome. )Tj /T1_1 1 Tf 0 -2.557 TD (Design)Tj /T1_0 1 Tf 0 -1.2 TD (Analysis of incremental cost effectiveness. )Tj /T1_1 1 Tf 0 -2.557 TD (Setting)Tj /T1_0 1 Tf 0 -1.2 TD (United Kingdom. )Tj /T1_1 1 Tf 0 -2.557 TD (Main outcome measures)Tj /T1_0 1 Tf 0 -1.2 TD (Number of liveborn babies with Down's syndrome, miscarriages due to chor\ ionic villus sampling or amniocentesis, )Tj T* (healthcare costs of screening programme, and additional costs and additi\ onal miscarriages per additional affected )Tj T* (live birth prevented by adopting a more effective strategy. )Tj /T1_1 1 Tf 0 -2.557 TD (Results)Tj /T1_0 1 Tf 0 -1.2 TD (Compared with no screening, the additional cost per additional liveborn \ baby with Down's syndrome prevented )Tj T* (was \24322)Tj 3.519 0 Td (000 for measurement of nuchal translucency. The cost of the integrated t\ est was \24351)Tj 33.929 0 Td (000 compared with )Tj -37.449 -1.2 Td (measurement of nuchal translucency. All other strategies were more costl\ y and less effective, or cost more per )Tj T* (additional affected baby prevented. Depending on the cost of the screeni\ ng test, the first trimester combined test )Tj ET EMC /Artifact <>BDC Q 0 0 0 rg BT /T1_0 1 Tf 6.4121 0 0 6.4121 18 9.1339 Tm (http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=37550 \(1 of 9\ \)8.2.2007 11:14:34)Tj ET EMC endstream endobj 394 0 obj<>stream /Artifact <>BDC 0 0 0 rg 0 i BT /T1_0 1 Tf 0 Tc 0 Tw 0 Ts 100 Tz 0 Tr 6.4121 0 0 6.4121 18 782.1339 Tm (Screening for Down's syndrome: effects, safety, and cost effectiveness o\ f first and second trimester strategies)Tj ET EMC /WebCaptureBG BMC /WebCaptureFN <>BDC q 0 18 612 756 re W* n /Artifact <>BDC Q 0.973 0.973 0.973 rg 7.125 18 604.875 756 re f EMC q 0 18 612 756 re W* n /Artifact <>BDC Q 0.882 0.882 0.882 rg 131.804 422.56 461.672 246.139 re f 0.376 0.812 1 rg 131.092 669.411 m 594.189 669.411 l 593.476 668.699 l 131.804 668.699 l h f 131.092 669.411 m 131.092 421.847 l 131.804 422.56 l 131.804 668.699 l h f 594.189 669.411 m 594.189 421.847 l 593.476 422.56 l 593.476 668.699 l h 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94.044 13.537 re W* n 0.753 0.753 0.753 RG 0.712 w 10 M 0 j 1 J [0 1.425]0.713 d 18.524 331.899 m 112.568 331.899 l S EMC Q q 0 18 612 756 re W* n /Artifact <>BDC Q q 18.524 318.007 94.044 13.537 re W* n 0.753 0.753 0.753 RG 0.712 w 10 M 0 j 1 J [0 1.425]0.713 d 18.524 318.363 m 112.568 318.363 l S EMC Q q 0 18 612 756 re W* n /Artifact <>BDC Q q 18.524 295.564 94.044 22.442 re W* n 0.753 0.753 0.753 RG 0.712 w 10 M 0 j 1 J [0 1.425]0.713 d 18.524 295.92 m 112.568 295.92 l S EMC Q q 0 18 612 756 re W* n /Artifact <>BDC Q q 18.524 282.028 94.044 13.537 re W* n 0.753 0.753 0.753 RG 0.712 w 10 M 0 j 1 J [0 1.425]0.713 d 18.524 282.384 m 112.568 282.384 l S EMC Q q 0 18 612 756 re W* n /Artifact <>BDC Q q 18.524 268.491 94.044 13.537 re W* n 0.753 0.753 0.753 RG 0.712 w 10 M 0 j 1 J [0 1.425]0.713 d 18.524 268.847 m 112.568 268.847 l S EMC Q q 0 18 612 756 re W* n /Artifact <>BDC Q 0 0.447 0.659 rg 131.983 383.389 463.097 15.66 re f 131.092 399.939 m 595.97 399.939 l 595.079 399.048 l 131.983 399.048 l h f 131.092 399.939 m 131.092 382.498 l 131.983 383.389 l 131.983 399.048 l h f 595.97 399.939 m 595.97 382.498 l 595.079 383.389 l 595.079 399.048 l h f 131.092 382.498 m 595.97 382.498 l 595.079 383.389 l 131.983 383.389 l h f EMC q 0 18 612 756 re W* n /Artifact <>BDC Q 0 0.467 0.667 rg 9.262 215.014 m 112.568 215.014 l 112.568 214.302 l 9.262 214.302 l h f EMC q 0 18 612 756 re W* n /Artifact <>BDC Q q 18.524 200.765 94.044 13.537 re W* n 0.753 0.753 0.753 RG 0.712 w 10 M 0 j 1 J [0 1.425]0.713 d 18.524 201.121 m 112.568 201.121 l S EMC Q q 0 18 612 756 re W* n /Artifact <>BDC Q q 18.524 187.229 94.044 13.537 re W* n 0.753 0.753 0.753 RG 0.712 w 10 M 0 j 1 J [0 1.425]0.713 d 18.524 187.585 m 112.568 187.585 l S EMC Q q 0 18 612 756 re W* n /Artifact <>BDC Q q 18.524 173.692 94.044 13.537 re W* n 0.753 0.753 0.753 RG 0.712 w 10 M 0 j 1 J [0 1.425]0.713 d 18.524 174.048 m 112.568 174.048 l S EMC Q q 0 18 612 756 re W* n /Artifact <>BDC Q q 11.399 160.155 101.169 13.537 re W* n 0.753 0.753 0.753 RG 0.712 w 10 M 0 j 1 J [0 1.425]0.713 d 11.399 160.511 m 112.568 160.511 l S EMC Q q 0 18 612 756 re W* n /Artifact <>BDC Q q 18.524 146.619 94.044 13.537 re W* n 0.753 0.753 0.753 RG 0.712 w 10 M 0 j 1 J [0 1.425]0.713 d 18.524 146.975 m 112.568 146.975 l S EMC Q q 0 18 612 756 re W* n /Artifact <>BDC Q q 18.524 133.082 94.044 13.537 re W* n 0.753 0.753 0.753 RG 0.712 w 10 M 0 j 1 J [0 1.425]0.713 d 18.524 133.438 m 112.568 133.438 l S EMC Q q 0 18 612 756 re W* n /Artifact <>BDC Q q 18.524 110.639 94.044 22.442 re W* n 0.753 0.753 0.753 RG 0.712 w 10 M 0 j 1 J [0 1.425]0.713 d 18.524 110.996 m 112.568 110.996 l S EMC Q q 0 18 612 756 re W* n /Artifact <>BDC Q q 18.524 97.103 94.044 13.537 re W* n 0.753 0.753 0.753 RG 0.712 w 10 M 0 j 1 J [0 1.425]0.713 d 18.524 97.459 m 112.568 97.459 l S EMC Q q 0 18 612 756 re W* n /Artifact <>BDC Q q 18.524 83.566 94.044 13.537 re W* n 0.753 0.753 0.753 RG 0.712 w 10 M 0 j 1 J [0 1.425]0.713 d 18.524 83.922 m 112.568 83.922 l S EMC Q q 0 18 612 756 re W* n /Artifact <>BDC Q 0 0.447 0.659 rg 131.983 198.464 463.097 15.66 re f 131.092 215.014 m 595.97 215.014 l 595.079 214.124 l 131.983 214.124 l h f 131.092 215.014 m 131.092 197.573 l 131.983 198.464 l 131.983 214.124 l h f 595.97 215.014 m 595.97 197.573 l 595.079 198.464 l 595.079 214.124 l h f 131.092 197.573 m 595.97 197.573 l 595.079 198.464 l 131.983 198.464 l h f EMC q 0 18 612 756 re W* n /Artifact <>BDC Q /CS0 cs /P0 scn 114.705 30.824 14.249 737.476 re f EMC EMC EMC /Article <>BDC q 0 18 612 756 re W* n 0 0 0 rg BT /T1_0 1 Tf 9.9744 0 0 9.9744 131.092 759.7335 Tm (and the quadruple test would also be cost effective options. )Tj /T1_1 1 Tf 0 -2.557 TD (Conclusions)Tj /T1_0 1 Tf 0 -1.2 TD (The choice of screening strategy should be between the integrated test, \ first trimester combined test, quadruple )Tj T* (test, or nuchal translucency measurement depending on how much service p\ roviders are willing to pay, the total )Tj T* (budget available, and values on safety. Screening based on maternal age,\ the second trimester double test, and the )Tj T* (first trimester serum test was less effective, less safe, and more costl\ y than these four options. )Tj /TT0 1 Tf 10.4731 0 0 10.4731 141.0664 650.7578 Tm (What is already known on this topic)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 141.0664 624.7657 Tm (Screening strategies that combine nuchal translucency measurement with s\ erum testing perform better than )Tj T* (either of these tests used alone)Tj 0 -2.557 TD (Serum testing in the second trimester using the triple test is cost effe\ ctive compared with screening based on )Tj 0 -1.2 TD (maternal age)Tj /TT0 1 Tf 10.4731 0 0 10.4731 141.0664 549.703 Tm (What this study adds)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 141.0664 523.7109 Tm (The integrated test is the most effective, safest, and most expensive st\ rategy)Tj 0 -2.557 TD (The choice of screening strategy should be between the integrated test, \ first trimester combined test, )Tj 0 -1.2 TD (quadruple test, or measurement of nuchal translucency)Tj 0 -2.557 TD (Screening based on maternal age, the second trimester double test, and t\ he first trimester serum test is less )Tj 0 -1.2 TD (effective, less safe, and more costly than the above options )Tj 0 0.251 0.502 rg /TT1 1 Tf 7.4808 0 0 7.4808 22.0862 391.6571 Tm (Top)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 34.9756 391.6571 Tm ( )Tj /TT1 1 Tf 7.4808 0 0 7.4808 22.0862 378.1205 Tm (Abstract)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 49.5257 378.1205 Tm ( )Tj ET q 3.5622864 0 0 7.1245575 14.9615784 362.8913116 cm /Im0 Do Q 0.502 0.502 0.502 rg BT /TT1 1 Tf 7.4808 0 0 7.4808 18.5239 364.5838 Tm (Introduction)Tj 0 0 1 rg /T1_0 1 Tf 9.9744 0 0 9.9744 57.611 364.5838 Tm ( )Tj 0 0.251 0.502 rg /TT1 1 Tf 7.4808 0 0 7.4808 22.0862 351.0471 Tm (Methods)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 50.775 351.0471 Tm ( )Tj /TT1 1 Tf 7.4808 0 0 7.4808 22.0862 337.5105 Tm (Results)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 47.0271 337.5105 Tm ( )Tj /TT1 1 Tf 7.4808 0 0 7.4808 22.0862 323.9738 Tm (Discussion)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 58.2483 323.9738 Tm ( )Tj /TT1 1 Tf 7.4808 0 0 7.4808 22.0862 312.3524 Tm (Commentary: Results may )Tj 0 -1.447 TD (not be widely applicable)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 101.5022 301.5314 Tm ( )Tj /TT1 1 Tf 7.4808 0 0 7.4808 22.0862 287.9947 Tm (Authors' response)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 82.1419 287.9947 Tm ( )Tj /TT1 1 Tf 7.4808 0 0 7.4808 22.0862 274.4581 Tm (References)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 60.3354 274.4581 Tm ( )Tj 1 1 1 rg /TT2 1 Tf 10.9718 0 0 10.9718 324.6138 387.6219 Tm (Introduction)Tj 0 0 0 rg /T1_0 1 Tf 9.9744 0 0 9.9744 131.092 360.3945 Tm (The provision of screening services in the NHS lags far behind advances \ in performance of screening tests over the )Tj 0 -1.56 TD (past decade.)Tj 0 0.314 0.627 rg 7.9795 0 0 7.9795 179.8368 349.9392 Tm (1)Tj 0 0 0 rg 9.9744 0 0 9.9744 183.8266 344.8323 Tm ( In 1998, 57% of antenatal care providers offered the second trimester d\ ouble test for Down's )Tj -5.287 -1.56 Td (syndrome and 8% offered screening based only on maternal age.)Tj 0 0.314 0.627 rg 7.9795 0 0 7.9795 389.2491 334.3769 Tm (2)Tj 0 0 0 rg 9.9744 0 0 9.9744 393.2389 329.27 Tm ( Few NHS providers offered the more effective )Tj -26.282 -1.2 Td (nuchal translucency measurement \(7%\) or quadruple test \(3%\). The int\ egrated test, which is the most effective )Tj T* (screening test and involves testing in the first and second trimesters,)Tj 0 0.314 0.627 rg 7.9795 0 0 7.9795 402.8641 306.8454 Tm (3)Tj 0 0 0 rg 9.9744 0 0 9.9744 406.8539 301.7385 Tm ( is available only privately.)Tj -27.647 -2.557 Td (The main considerations for providers of screening for Down's syndrome s\ hould be minimising the risk of babies )Tj 0 -1.2 TD (with Down's syndrome being missed by the test, reducing miscarriage due \ to amniocentesis or chorionic villus )Tj T* (sampling, and costs. We therefore compared the effects, safety, and cost\ effectiveness of nine strategies currently )Tj T* (available for screening for Down's syndrome in the United Kingdom.)Tj 0 0.251 0.502 rg /TT1 1 Tf 7.4808 0 0 7.4808 22.0862 206.7324 Tm (Top)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 34.9756 206.7324 Tm ( )Tj /TT1 1 Tf 7.4808 0 0 7.4808 22.0862 193.1958 Tm (Abstract)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 49.5257 193.1958 Tm ( )Tj /TT1 1 Tf 7.4808 0 0 7.4808 22.0862 179.6591 Tm (Introduction)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 61.1733 179.6591 Tm ( )Tj ET q 3.5622864 0 0 7.1245575 14.9615784 164.4299469 cm /Im0 Do Q 0.502 0.502 0.502 rg BT /TT1 1 Tf 7.4808 0 0 7.4808 18.5239 166.1224 Tm (Methods)Tj 0 0 1 rg /T1_0 1 Tf 9.9744 0 0 9.9744 47.2127 166.1224 Tm ( )Tj 0 0.251 0.502 rg /TT1 1 Tf 7.4808 0 0 7.4808 22.0862 152.5858 Tm (Results)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 47.0271 152.5858 Tm ( )Tj /TT1 1 Tf 7.4808 0 0 7.4808 22.0862 139.0491 Tm (Discussion)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 58.2483 139.0491 Tm ( )Tj /TT1 1 Tf 7.4808 0 0 7.4808 22.0862 127.4277 Tm (Commentary: Results may )Tj 0 -1.447 TD (not be widely applicable)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 101.5022 116.6067 Tm ( )Tj /TT1 1 Tf 7.4808 0 0 7.4808 22.0862 103.07 Tm (Authors' response)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 82.1419 103.07 Tm ( )Tj /TT1 1 Tf 7.4808 0 0 7.4808 22.0862 89.5334 Tm (References)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 60.3354 89.5334 Tm ( )Tj 1 1 1 rg /TT2 1 Tf 10.9718 0 0 10.9718 337.4234 202.6972 Tm (Methods)Tj 0 0 0 rg /T1_1 1 Tf 11.9693 0 0 11.9693 131.092 173.7565 Tm (Decision model)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 131.092 161.1067 Tm (We compared no screening with nine screening strategies offered in the f\ irst or second trimesters \(table )Tj 0 0.314 0.627 rg (1)Tj 0 0 0 rg (\). )Tj 0 -1.343 TD (Prenatal diagnosis included abdominal chorionic villus sampling before 1\ 5 weeks' gestation or amniocentesis )Tj 0 -1.2 TD (thereafter if screening indicated a greater than 1 in 300 risk of Down's\ syndrome. We determined the number of )Tj 0 -1.2 TD (liveborn children with and without Down's syndrome, pregnancy losses \(i\ ncluding terminations, spontaneous )Tj 0 -1.2 TD (losses, and miscarriages due to chorionic villus sampling or amniocentes\ is\), and the healthcare cost of the )Tj T* (screening programme in 10)Tj 11.184 0 Td (000 women with the age distribution of women delivering in England and W\ ales in )Tj -11.184 -1.2 Td (1995. )Tj /T1_1 1 Tf 11.9693 0 0 11.9693 131.092 60.6469 Tm (Model estimates)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 131.092 44.4042 Tm (Estimates used in the model are based on a systematic review,)Tj 0 0.314 0.627 rg 7.9795 0 0 7.9795 379.0253 49.5111 Tm (1)Tj 0 0 0 rg 9.9744 0 0 9.9744 383.0151 44.4042 Tm ( other published sources, and discussions with a )Tj -25.257 -1.2 Td (reference group of UK service providers and users \(see acknowledgements\ \). We assumed that 100% of women )Tj ET EMC /Artifact <>BDC Q 0 0 0 rg BT /T1_0 1 Tf 6.4121 0 0 6.4121 18 9.1339 Tm (http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=37550 \(2 of 9\ \)8.2.2007 11:14:34)Tj ET EMC endstream endobj 395 0 obj<> endobj 396 0 obj<>stream /Artifact <>BDC 0 0 0 rg 0 i BT /T1_0 1 Tf 0 Tc 0 Tw 0 Ts 100 Tz 0 Tr 6.4121 0 0 6.4121 18 782.1339 Tm (Screening for Down's syndrome: effects, safety, and cost effectiveness o\ f first and second trimester strategies)Tj ET EMC /WebCaptureBG BMC /WebCaptureFN <>BDC q 0 18 612 756 re W* n /Artifact <>BDC Q 0.973 0.973 0.973 rg 7.125 18 604.875 756 re f EMC q 0 18 612 756 re W* n /Artifact <>BDC Q 0 0.467 0.667 rg 9.262 189.131 m 112.568 189.131 l 112.568 188.419 l 9.262 188.419 l h f EMC q 0 18 612 756 re W* n /Artifact <>BDC Q q 18.524 174.882 94.044 13.537 re W* n 0.753 0.753 0.753 RG 0.712 w 10 M 0 j 1 J [0 1.425]0.713 d 18.524 175.238 m 112.568 175.238 l S EMC Q q 0 18 612 756 re W* n /Artifact <>BDC Q q 18.524 161.345 94.044 13.537 re W* n 0.753 0.753 0.753 RG 0.712 w 10 M 0 j 1 J [0 1.425]0.713 d 18.524 161.701 m 112.568 161.701 l S EMC Q q 0 18 612 756 re W* n /Artifact <>BDC Q q 18.524 147.809 94.044 13.537 re W* n 0.753 0.753 0.753 RG 0.712 w 10 M 0 j 1 J [0 1.425]0.713 d 18.524 148.165 m 112.568 148.165 l S EMC Q q 0 18 612 756 re W* n /Artifact <>BDC Q q 18.524 134.272 94.044 13.537 re W* n 0.753 0.753 0.753 RG 0.712 w 10 M 0 j 1 J [0 1.425]0.713 d 18.524 134.628 m 112.568 134.628 l S EMC Q q 0 18 612 756 re W* n /Artifact <>BDC Q q 11.399 120.735 101.169 13.537 re W* n 0.753 0.753 0.753 RG 0.712 w 10 M 0 j 1 J [0 1.425]0.713 d 11.399 121.091 m 112.568 121.091 l S EMC Q q 0 18 612 756 re W* n /Artifact <>BDC Q q 18.524 107.199 94.044 13.537 re W* n 0.753 0.753 0.753 RG 0.712 w 10 M 0 j 1 J [0 1.425]0.713 d 18.524 107.555 m 112.568 107.555 l S EMC Q q 0 18 612 756 re W* n /Artifact <>BDC Q q 18.524 84.756 94.044 22.442 re W* n 0.753 0.753 0.753 RG 0.712 w 10 M 0 j 1 J [0 1.425]0.713 d 18.524 85.112 m 112.568 85.112 l S EMC Q q 0 18 612 756 re W* n /Artifact <>BDC Q q 18.524 71.22 94.044 13.537 re W* n 0.753 0.753 0.753 RG 0.712 w 10 M 0 j 1 J [0 1.425]0.713 d 18.524 71.576 m 112.568 71.576 l S EMC Q q 0 18 612 756 re W* n /Artifact <>BDC Q q 18.524 57.683 94.044 13.537 re W* n 0.753 0.753 0.753 RG 0.712 w 10 M 0 j 1 J [0 1.425]0.713 d 18.524 58.039 m 112.568 58.039 l S EMC Q q 0 18 612 756 re W* n /Artifact <>BDC Q 0 0.447 0.659 rg 131.983 172.581 463.097 15.66 re f 131.092 189.131 m 595.97 189.131 l 595.079 188.24 l 131.983 188.24 l h f 131.092 189.131 m 131.092 171.69 l 131.983 172.581 l 131.983 188.24 l h f 595.97 189.131 m 595.97 171.69 l 595.079 172.581 l 595.079 188.24 l h f 131.092 171.69 m 595.97 171.69 l 595.079 172.581 l 131.983 172.581 l h f EMC q 0 18 612 756 re W* n /Artifact <>BDC Q /CS0 cs /P0 scn 114.705 30.824 14.249 737.476 re f EMC EMC EMC /Article <>BDC q 0 18 612 756 re W* n 0 0 0 rg BT /T1_0 1 Tf 9.9744 0 0 9.9744 131.092 757.9418 Tm (attend antenatal clinic between 10 and 14 completed weeks of gestation \(\ median 12 weeks gestation\) and are )Tj 0 -1.2 TD (offered tests in the first trimester or between 15 and 19 weeks \(median\ 15 weeks\) for tests in the second trimester. )Tj T* (Table )Tj 0 0.314 0.627 rg (1)Tj 0 0 0 rg ( gives the time required for counselling and for processing of screening\ and diagnostic tests and the )Tj 0 -1.343 TD (proportion of women accepting procedures. )Tj 0 -2.557 TD (Based on the age specific prevalence of pregnancies affected by Down's s\ yndrome at 10 and 16 weeks' gestation )Tj 0 -1.56 TD (and at term,)Tj 0 0.314 0.627 rg 7.9795 0 0 7.9795 178.4603 684.6478 Tm (6)Tj 0 0 0 rg 0.5 -0.32 Td (,)Tj 0 0.314 0.627 rg 0.25 0.32 Td (10)Tj 0 0 0 rg 9.9744 0 0 9.9744 192.4245 679.5409 Tm ( we took account of the weekly risk of spontaneous fetal loss in affecte\ d and unaffected )Tj -6.149 -1.2 Td (pregnancies. Overall, we estimated that 45% of affected fetuses would be\ spontaneously lost between 10 weeks' )Tj 0 -1.2 TD (gestation and term. The test characteristics for nuchal translucency mea\ surements were derived from a study of )Tj 0 -1.56 TD (326 affected fetuses and 95)Tj 11.155 0 Td (476 unaffected fetuses,)Tj 0 0.314 0.627 rg 7.9795 0 0 7.9795 334.5923 645.147 Tm (4)Tj 0 0 0 rg 0.5 -0.32 Td (,)Tj 0 0.314 0.627 rg 0.25 0.32 Td (11)Tj 0 0 0 rg 9.9744 0 0 9.9744 348.5564 640.0401 Tm ( adjusted for verification bias due to termination of affected )Tj -21.802 -1.56 Td (fetuses who would otherwise have been spontaneously lost.)Tj 0 0.314 0.627 rg 7.9795 0 0 7.9795 368.7816 629.5847 Tm (4)Tj 0 0 0 rg 9.9744 0 0 9.9744 131.092 598.9719 Tm (The test characteristics for all serum tests were derived from the analy\ sis of stored serum samples from 77 women )Tj T* (with affected pregnancies and 385 with unaffected pregnancies, all of wh\ om had amniocentesis.)Tj 0 0.314 0.627 rg 7.9795 0 0 7.9795 514.4576 588.5165 Tm (6)Tj 0 0 0 rg 9.9744 0 0 9.9744 518.4474 583.4096 Tm ( We selected )Tj -38.835 -1.56 Td (combinations of serum analytes that, according to the systematic review,\ )Tj 0 0.314 0.627 rg 7.9795 0 0 7.9795 421.1372 572.9542 Tm (6)Tj 0 0 0 rg 9.9744 0 0 9.9744 425.127 567.8473 Tm ( performed best. Alternative )Tj -29.479 -1.291 Td (combinations of analytes\227for example, substitution of free )Tj /T1_1 1 Tf (b)Tj /T1_0 1 Tf ( human chorionic gonadotrophin for total human )Tj 0 -1.2 TD (chorionic gonadotrophin or inhibin A for unconjugated oestriol, would no\ t substantially affect test performance. )Tj T* (We assumed that all women would have an ultrasound dating scan and that,\ for second trimester serum tests, )Tj T* (maternal weight would be taken into account.)Tj 0 -2.557 TD (We estimated the risk of giving birth to a Down's syndrome baby for each\ woman, based on the screening test )Tj 0 -1.2 TD (results and maternal age. Firstly, we calculated the distribution of lik\ elihood ratios for the screening test separately )Tj 0 -1.56 TD (for pregnancies affected and unaffected by Down's syndrome using Monte C\ arlo simulation)Tj 0 0.314 0.627 rg 7.9795 0 0 7.9795 497.7106 471.1309 Tm (12)Tj 0 0 0 rg 9.9744 0 0 9.9744 505.6901 466.024 Tm ( and assumed )Tj -37.556 -1.2 Td (independence between the nuchal translucency measurement, first trimeste\ r serum test \(PAPP-A\), and quadruple )Tj 0 -1.2 TD (test. We then calculated the distributions of risk of an affected pregna\ ncy for each year of maternal age by )Tj T* (multiplying likelihood ratios by the age specific risk of an affected li\ ve birth. Finally, we calculated a single, age )Tj T* (specific distribution of risk after screening by taking account of the p\ roportion of pregnant women at each )Tj T* (maternal age and the age specific risk of Down's syndrome.)Tj /T1_2 1 Tf 11.9693 0 0 11.9693 131.092 378.9584 Tm (Cost)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 131.092 366.3086 Tm (The costs of screening tests included laboratory expenses \(consumables \ and staff\), informing the women of the )Tj T* (results \(by telephone if positive, by post if negative\), service costs\ \(including processing results and monitoring the )Tj T* (service\), overheads, and \(for nuchal translucency measurement\) traini\ ng \(table )Tj 0 0.314 0.627 rg (1)Tj 0 0 0 rg (\). The costs of chorionic villus )Tj 0 -1.343 TD (sampling and amniocentesis included counselling before the procedure, eq\ uipment and staff to do the procedure, )Tj 0 -1.2 TD (laboratory expenses \(consumables and staff, non-reagent and labour cost\ s\), and overheads. For all these costs, we )Tj 0 -1.2 TD (assumed an existing infrastructure for antenatal screening and diagnosis\ of Down's syndrome. We also estimated )Tj T* (costs of events arising from screening \(table )Tj 0 0.314 0.627 rg (2)Tj 0 0 0 rg (\) All costs were adjusted to June 1998 prices \(for full details see )Tj ET 0 0.314 0.627 RG 0.503 w 10 M 0 j 0 J []0 d 131.092 278.166 m 223.614 278.166 l S 0 0.314 0.627 rg BT /T1_0 1 Tf 9.9744 0 0 9.9744 131.092 279.674 Tm (www.ich.ucl.ac.uk/srtu)Tj 0 0 0 rg (\). )Tj /T1_2 1 Tf 11.9693 0 0 11.9693 131.092 251.0297 Tm (Sensitivity analyses)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 131.092 238.38 Tm (The sensitivity analyses examined the effect of a 50% increase and decre\ ase in the costs of chorionic villus )Tj T* (sampling, amniocentesis, the screening test, and nuchal translucency mea\ surement. We also tested the effect of )Tj T* (varying the cut-off point for a positive result. )Tj 0 0.251 0.502 rg /TT0 1 Tf 7.4808 0 0 7.4808 22.0862 180.8491 Tm (Top)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 34.9756 180.8491 Tm ( )Tj /TT0 1 Tf 7.4808 0 0 7.4808 22.0862 167.3125 Tm (Abstract)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 49.5257 167.3125 Tm ( )Tj /TT0 1 Tf 7.4808 0 0 7.4808 22.0862 153.7758 Tm (Introduction)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 61.1733 153.7758 Tm ( )Tj /TT0 1 Tf 7.4808 0 0 7.4808 22.0862 140.2391 Tm (Methods)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 50.775 140.2391 Tm ( )Tj ET q 3.5622864 0 0 7.1245575 14.9615784 125.009964 cm /Im0 Do Q 0.502 0.502 0.502 rg BT /TT0 1 Tf 7.4808 0 0 7.4808 18.5239 126.7024 Tm (Results)Tj 0 0 1 rg /T1_0 1 Tf 9.9744 0 0 9.9744 43.4648 126.7024 Tm ( )Tj 0 0.251 0.502 rg /TT0 1 Tf 7.4808 0 0 7.4808 22.0862 113.1658 Tm (Discussion)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 58.2483 113.1658 Tm ( )Tj /TT0 1 Tf 7.4808 0 0 7.4808 22.0862 101.5444 Tm (Commentary: Results may )Tj 0 -1.447 TD (not be widely applicable)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 101.5022 90.7234 Tm ( )Tj /TT0 1 Tf 7.4808 0 0 7.4808 22.0862 77.1867 Tm (Authors' response)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 82.1419 77.1867 Tm ( )Tj /TT0 1 Tf 7.4808 0 0 7.4808 22.0862 63.6501 Tm (References)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 60.3354 63.6501 Tm ( )Tj 1 1 1 rg /TT1 1 Tf 10.9718 0 0 10.9718 340.8082 176.8138 Tm (Results)Tj 0 0 0 rg /T1_2 1 Tf 11.9693 0 0 11.9693 131.092 147.8732 Tm (Effects and costs)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 131.092 135.2234 Tm (Table )Tj 0 0.314 0.627 rg (3)Tj 0 0 0 rg ( and the figure show the effects and costs of no screening and of the ni\ ne screening strategies. )Tj 0 -1.343 TD (Measurement of nuchal translucency would result in 7.6 fewer births of b\ abies with Down's syndrome compared )Tj 0 -1.2 TD (with no antenatal screening, at a total cost of \243171)Tj 20.322 0 Td (000 per 10)Tj 4.491 0 Td (000 pregnant women. The incremental cost )Tj -24.814 -1.2 Td (effectiveness ratio for nuchal translucency compared with no screening i\ s \24322)Tj 31.373 0 Td (000 \(171)Tj 3.797 0 Td (000/7.6\) per prevented )Tj -35.171 -1.2 Td (birth of a baby with Down's syndrome. The integrated test results in 2.0\ fewer births of babies with Down's )Tj T* (syndrome than the nuchal translucency measurement at a total cost of \243\ 276)Tj 30.292 0 Td (000. The incremental cost effectiveness )Tj -30.292 -1.291 Td (ratio of the integrated test compared with nuchal translucency is \24352\ )Tj 27.598 0 Td (000 \(276)Tj 3.797 0 Td (000)Tj /T1_1 1 Tf (-)Tj /T1_0 1 Tf (171)Tj 3.763 0 Td (000\)/2.0\) per affected baby )Tj -35.159 -1.2 Td (prevented. )Tj ET EMC /Artifact <>BDC Q 0 0 0 rg BT /T1_0 1 Tf 6.4121 0 0 6.4121 18 9.1339 Tm (http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=37550 \(3 of 9\ \)8.2.2007 11:14:34)Tj ET EMC endstream endobj 397 0 obj<>stream /Artifact <>BDC 0 0 0 rg 0 i BT /T1_0 1 Tf 0 Tc 0 Tw 0 Ts 100 Tz 0 Tr 6.4121 0 0 6.4121 18 782.1339 Tm (Screening for Down's syndrome: effects, safety, and cost effectiveness o\ f first and second trimester strategies)Tj ET EMC /WebCaptureBG BMC /WebCaptureFN <>BDC q 0 18 612 756 re W* n /Artifact <>BDC Q 0.973 0.973 0.973 rg 7.125 18 604.875 756 re f EMC q 0 18 612 756 re W* n /Artifact <>BDC Q 0 0.467 0.667 rg 9.262 337.499 m 112.568 337.499 l 112.568 336.787 l 9.262 336.787 l h f EMC q 0 18 612 756 re W* n /Artifact <>BDC Q q 18.524 323.25 94.044 13.537 re W* n 0.753 0.753 0.753 RG 0.712 w 10 M 0 j 1 J [0 1.425]0.713 d 18.524 323.606 m 112.568 323.606 l S EMC Q q 0 18 612 756 re W* n /Artifact <>BDC Q q 18.524 309.714 94.044 13.537 re W* n 0.753 0.753 0.753 RG 0.712 w 10 M 0 j 1 J [0 1.425]0.713 d 18.524 310.07 m 112.568 310.07 l S EMC Q q 0 18 612 756 re W* n /Artifact <>BDC Q q 18.524 296.177 94.044 13.537 re W* n 0.753 0.753 0.753 RG 0.712 w 10 M 0 j 1 J [0 1.425]0.713 d 18.524 296.533 m 112.568 296.533 l S EMC Q q 0 18 612 756 re W* n /Artifact <>BDC Q q 18.524 282.64 94.044 13.537 re W* n 0.753 0.753 0.753 RG 0.712 w 10 M 0 j 1 J [0 1.425]0.713 d 18.524 282.996 m 112.568 282.996 l S EMC Q q 0 18 612 756 re W* n /Artifact <>BDC Q q 18.524 269.104 94.044 13.537 re W* n 0.753 0.753 0.753 RG 0.712 w 10 M 0 j 1 J [0 1.425]0.713 d 18.524 269.46 m 112.568 269.46 l S EMC Q q 0 18 612 756 re W* n /Artifact <>BDC Q q 11.399 255.567 101.169 13.537 re W* n 0.753 0.753 0.753 RG 0.712 w 10 M 0 j 1 J [0 1.425]0.713 d 11.399 255.923 m 112.568 255.923 l S EMC Q q 0 18 612 756 re W* n /Artifact <>BDC Q q 18.524 233.125 94.044 22.442 re W* n 0.753 0.753 0.753 RG 0.712 w 10 M 0 j 1 J [0 1.425]0.713 d 18.524 233.481 m 112.568 233.481 l S EMC Q q 0 18 612 756 re W* n /Artifact <>BDC Q q 18.524 219.588 94.044 13.537 re W* n 0.753 0.753 0.753 RG 0.712 w 10 M 0 j 1 J [0 1.425]0.713 d 18.524 219.944 m 112.568 219.944 l S EMC Q q 0 18 612 756 re W* n /Artifact <>BDC Q q 18.524 206.051 94.044 13.537 re W* n 0.753 0.753 0.753 RG 0.712 w 10 M 0 j 1 J [0 1.425]0.713 d 18.524 206.407 m 112.568 206.407 l S EMC Q q 0 18 612 756 re W* n /Artifact <>BDC Q 0 0.447 0.659 rg 131.983 320.949 463.097 15.66 re f 131.092 337.499 m 595.97 337.499 l 595.079 336.609 l 131.983 336.609 l h f 131.092 337.499 m 131.092 320.058 l 131.983 320.949 l 131.983 336.609 l h f 595.97 337.499 m 595.97 320.058 l 595.079 320.949 l 595.079 336.609 l h f 131.092 320.058 m 595.97 320.058 l 595.079 320.949 l 131.983 320.949 l h f EMC q 0 18 612 756 re W* n /Artifact <>BDC Q /CS0 cs /P0 scn 114.705 30.824 14.249 737.476 re f EMC EMC EMC /Article <>BDC q 0 18 612 756 re W* n 0 0 0 rg BT /T1_0 1 Tf 9.9744 0 0 9.9744 131.092 759.7335 Tm (Service providers with an intermediate total budget should consider the \ first trimester combined test or the )Tj 0 -1.2 TD (quadruple test. Compared with measuring nuchal translucency, the first t\ rimester combined test costs an extra )Tj T* (\24357)Tj 1.714 0 Td (000 per affected liveborn baby prevented \(total cost \243238)Tj 23.153 0 Td (000\). At a similar total cost \(\243241)Tj 13.741 0 Td (000\), the )Tj -38.609 -1.2 Td (quadruple test costs an additional \24375)Tj 15.296 0 Td (000 per affected baby prevented compared with measuring nuchal )Tj -15.296 -1.2 Td (translucency.)Tj /T1_1 1 Tf 11.9693 0 0 11.9693 131.092 684.6371 Tm (Effects and safety)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 131.092 671.9873 Tm (The integrated test is the most effective and safest strategy. All other\ strategies result in more liveborn babies with )Tj T* (Down's syndrome and more miscarriages of unaffected pregnancies due to a\ mniocentesis or chorionic villus )Tj T* (sampling. Compared with no screening, the integrated test results in 0.1\ 4 miscarriages due to chorionic villus )Tj T* (sampling or amniocentesis per birth of a Down's syndrome baby prevented.\ The next safest strategies, compared )Tj T* (with no screening, are the first trimester combined test \(0.22 miscarri\ ages\), nuchal translucency measurement )Tj T* (\(0.34\), and the quadruple test \(0.42\). )Tj /T1_1 1 Tf 11.9693 0 0 11.9693 131.092 584.9217 Tm (Sensitivity analyses)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 131.092 572.2719 Tm (A 50% increase or decrease in the unit costs of chorionic villus samplin\ g and amniocentesis would hardly alter the )Tj T* (cost effectiveness. If the cost of amniocentesis fell by 50%, the quadru\ ple test would enter the efficiency frontier )Tj T* (\(cost effectiveness ratio compared with nuchal translucency \24339)Tj 25.902 0 Td (000 and for the integrated test compared with the )Tj -25.902 -1.2 Td (quadruple test \24351)Tj 7.602 0 Td (000\). )Tj -7.602 -2.557 Td (The cost effectiveness of the screening strategies is most susceptible t\ o variation in the costs of the screening test. )Tj T* (A 50% decrease in the unit costs of all screening tests would increase t\ he cost effectiveness ratio of all strategies )Tj T* (above that of the integrated test \(\24319)Tj 14.878 0 Td (000 compared with no screening\), although the cost effectiveness ratios\ )Tj -14.878 -1.2 Td (would be close for nuchal translucency measurement and the first trimest\ er combined test. A 50% increase in the )Tj T* (unit costs of measuring nuchal translucency would increase the cost effe\ ctiveness ratio for nuchal translucency )Tj 0 -1.2 TD (compared with no screening to \24325)Tj 14.295 0 Td (000. The cost effectiveness ratios for the first trimester combined, qua\ druple, )Tj -14.295 -1.2 Td (and integrated tests would be similar \(\24351)Tj 16.99 0 Td (000-\24356)Tj 3.547 0 Td (000\). The second trimester double test, triple test, maternal age, )Tj -20.538 -1.2 Td (and first trimester serum test were not cost effective at any of the ass\ umptions tested.)Tj 0 -2.557 TD (Varying the cut-off point for doing amniocentesis or chorionic villus sa\ mpling between risks of 1 in 100 and 1 in )Tj 0 -1.2 TD (400 did not alter the cost effectiveness ranking of the screening strate\ gies. Similarly, varying the risk cut-off point )Tj T* (corresponding to a 5% false positive rate for the screening test did not\ alter the ranking \(see )Tj ET 0 0.314 0.627 RG 0.503 w 10 M 0 j 0 J []0 d 499.237 376.121 m 576.798 376.121 l S 0 0.314 0.627 rg BT /T1_0 1 Tf 9.9744 0 0 9.9744 499.2367 377.6289 Tm (www.ich.ucl.ac.uk/)Tj ET 131.092 362.727 m 146.054 362.727 l S BT /T1_0 1 Tf 9.9744 0 0 9.9744 131.092 364.2347 Tm (srtu)Tj 0 0 0 rg (\).)Tj 0 0.251 0.502 rg /TT0 1 Tf 7.4808 0 0 7.4808 22.0862 329.2175 Tm (Top)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 34.9756 329.2175 Tm ( )Tj /TT0 1 Tf 7.4808 0 0 7.4808 22.0862 315.6808 Tm (Abstract)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 49.5257 315.6808 Tm ( )Tj /TT0 1 Tf 7.4808 0 0 7.4808 22.0862 302.1441 Tm (Introduction)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 61.1733 302.1441 Tm ( )Tj /TT0 1 Tf 7.4808 0 0 7.4808 22.0862 288.6075 Tm (Methods)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 50.775 288.6075 Tm ( )Tj /TT0 1 Tf 7.4808 0 0 7.4808 22.0862 275.0708 Tm (Results)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 47.0271 275.0708 Tm ( )Tj ET q 3.5622864 0 0 7.1245575 14.9615784 259.841629 cm /Im0 Do Q 0.502 0.502 0.502 rg BT /TT0 1 Tf 7.4808 0 0 7.4808 18.5239 261.5341 Tm (Discussion)Tj 0 0 1 rg /T1_0 1 Tf 9.9744 0 0 9.9744 54.686 261.5341 Tm ( )Tj 0 0.251 0.502 rg /TT0 1 Tf 7.4808 0 0 7.4808 22.0862 249.9127 Tm (Commentary: Results may )Tj 0 -1.447 TD (not be widely applicable)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 101.5022 239.0917 Tm ( )Tj /TT0 1 Tf 7.4808 0 0 7.4808 22.0862 225.5551 Tm (Authors' response)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 82.1419 225.5551 Tm ( )Tj /TT0 1 Tf 7.4808 0 0 7.4808 22.0862 212.0184 Tm (References)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 60.3354 212.0184 Tm ( )Tj 1 1 1 rg /TT1 1 Tf 10.9718 0 0 10.9718 330.6593 325.1822 Tm (Discussion)Tj 0 0 0 rg /T1_0 1 Tf 9.9744 0 0 9.9744 131.092 297.9549 Tm (The nuchal translucency measurement, quadruple test, first trimester com\ bined, and integrated tests represent the )Tj 0 -1.2 TD (best options in terms of effectiveness, cost effectiveness, and safety. \ All other strategies would be less effective, )Tj T* (cost more per additional birth of an affected baby prevented, and be les\ s safe. This finding was robust in the )Tj T* (sensitivity analyses.)Tj 0 -2.557 TD (The choice between the four options depends on how much service provider\ s are willing to pay to prevent one )Tj 0 -1.2 TD (affected liveborn baby, on the total budget available for antenatal scre\ ening, and on how much service providers )Tj T* (value safety. We would expect service providers to be willing to spend a\ t least \24330)Tj 33.347 0 Td (000 to \24340)Tj 4.492 0 Td (000 per additional )Tj -37.84 -1.2 Td (affected baby prevented, as this reflects the incremental costs paid by \ most service providers that offer screening to )Tj 0 -1.56 TD (all women.)Tj 0 0.314 0.627 rg 7.9795 0 0 7.9795 175.4182 190.178 Tm (14)Tj 0 0 0 rg /T1_1 1 Tf 11.9693 0 0 11.9693 131.092 157.8518 Tm (Implications for practice)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 131.092 145.202 Tm (These findings contrast with current practice in the United Kingdom, whe\ re the second trimester double test is )Tj T* (most commonly offered.)Tj 0 0.314 0.627 rg 7.9795 0 0 7.9795 229.4394 134.7466 Tm (2)Tj 0 0 0 rg 9.9744 0 0 9.9744 233.4292 129.6398 Tm ( Moving from the double test to the first trimester combined test or qua\ druple test would )Tj -10.26 -1.2 Td (not cost any more and would result in 1.5 \(for the first trimester comb\ ined\) or 1.2 \(for the quadruple test\) fewer )Tj 0 -1.2 TD (affected liveborn babies for every 10)Tj 14.959 0 Td (000 pregnancies \(table )Tj 0 0.314 0.627 rg (2)Tj 0 0 0 rg (\). Alternatively, the nuchal translucency )Tj -14.959 -1.343 Td (measurement would be more effective than the double test \(0.3 fewer aff\ ected babies\) at a total cost saving of )Tj T* (\24370)Tj 1.714 0 Td (000. Finally, moving from the double test to the integrated test would r\ esult in 2.3 fewer affected babies and )Tj -1.714 -1.2 Td (cost \24313)Tj 3.575 0 Td (000 per additional affected baby prevented. )Tj -3.575 -2.557 Td (Limited research on women's preferences suggests that the choice of scre\ ening strategy should be based primarily )Tj ET EMC /Artifact <>BDC Q 0 0 0 rg BT /T1_0 1 Tf 6.4121 0 0 6.4121 18 9.1339 Tm (http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=37550 \(4 of 9\ \)8.2.2007 11:14:34)Tj ET EMC endstream endobj 398 0 obj<>stream /Artifact <>BDC 0 0 0 rg 0 i BT /T1_0 1 Tf 0 Tc 0 Tw 0 Ts 100 Tz 0 Tr 6.4121 0 0 6.4121 18 782.1339 Tm (Screening for Down's syndrome: effects, safety, and cost effectiveness o\ f first and second trimester strategies)Tj ET EMC /WebCaptureBG BMC /WebCaptureFN <>BDC q 0 18 612 756 re W* n /Artifact <>BDC Q 0.973 0.973 0.973 rg 7.125 18 604.875 756 re f EMC q 0 18 612 756 re W* n /Artifact <>BDC Q /CS0 cs /P0 scn 114.705 30.824 14.249 737.476 re f EMC EMC EMC /Article <>BDC q 0 18 612 756 re W* n 0 0 0 rg BT /T1_0 1 Tf 9.9744 0 0 9.9744 131.092 759.7335 Tm (on minimising the number of affected pregnancies that are missed and mis\ carriages due to chorionic villus )Tj 0 -1.56 TD (sampling or amniocentesis.)Tj 0 0.314 0.627 rg 7.9795 0 0 7.9795 239.9724 749.2781 Tm (15)Tj 0 0 0 rg 1 -0.32 Td (,)Tj 0 0.314 0.627 rg 0.25 0.32 Td (16)Tj 0 0 0 rg 9.9744 0 0 9.9744 257.9263 744.1712 Tm ( Timing of test results and termination seem to be a secondary considera\ tion. )Tj -12.716 -1.2 Td (Nevertheless, given the realistic distribution of gestation at attendanc\ e for antenatal screening that we used in our )Tj 0 -1.2 TD (analysis, only 31% of women would be in time for a surgical termination \ \(before 13 weeks gestation\) after nuchal )Tj T* (translucency or age based screening and none after the first trimester c\ ombined test \(see )Tj ET 0 0.314 0.627 RG 0.503 w 10 M 0 j 0 J []0 d 484.534 706.755 m 577.057 706.755 l S 0 0.314 0.627 rg BT /T1_0 1 Tf 9.9744 0 0 9.9744 484.5344 708.2634 Tm (www.ich.ucl.ac.uk/srtu)Tj 0 0 0 rg (\).)Tj /T1_1 1 Tf 11.9693 0 0 11.9693 131.092 679.6192 Tm (Implementation issues)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 131.092 666.9694 Tm (Our results are susceptible to variation in performance of screening tes\ ts. The performance of serum markers in )Tj 0 -1.56 TD (pregnancies affected by Down's syndrome is highly consistent across diff\ erent studies,)Tj 0 0.314 0.627 rg 7.9795 0 0 7.9795 476.6646 656.5141 Tm (1)Tj 0 0 0 rg 9.9744 0 0 9.9744 480.6544 651.4072 Tm ( whereas performance of )Tj -35.046 -1.56 Td (nuchal translucency measurement varies widely.)Tj 0 0.314 0.627 rg 7.9795 0 0 7.9795 324.7148 640.9518 Tm (17)Tj 0 0 0 rg 1 -0.32 Td (,)Tj 0 0.314 0.627 rg 0.25 0.32 Td (18)Tj 0 0 0 rg 9.9744 0 0 9.9744 342.6687 635.8449 Tm ( Such variation may be explained by verification bias, chance, )Tj -21.212 -1.56 Td (referral patterns, variation in test reliability,)Tj 0 0.314 0.627 rg 7.9795 0 0 7.9795 305.3346 625.3895 Tm (19)Tj 0 0 0 rg 9.9744 0 0 9.9744 313.3141 620.2826 Tm ( and the use of repeated measurements. We used performance )Tj -18.269 -1.2 Td (characteristics for nuchal translucency measurement derived from routine\ screening of 95)Tj 36.093 0 Td (000 pregnancies, which )Tj -36.093 -1.56 Td (were then adjusted for verification bias.)Tj 0 0.314 0.627 rg 7.9795 0 0 7.9795 289.5351 597.858 Tm (4)Tj 0 0 0 rg 9.9744 0 0 9.9744 293.5249 592.7511 Tm ( However, we do not know how much test performance was optimised by )Tj -16.285 -1.2 Td (repeated measurements or referral for a second opinion. In addition, the\ performance of the integrated test, which )Tj 0 -1.2 TD (was derived by combining test characteristics for serum tests and the nu\ chal translucency measurement from )Tj T* (different datasets, needs to be evaluated in a study of pregnant women. \ )Tj 0 -2.557 TD (A further concern, examined in the sensitivity analysis, is the possibil\ ity of an increased relative risk of )Tj 0 -1.2 TD (spontaneous miscarriage in women with a positive test result \(>1 in 300\ risk of Down's syndrome\) compared with )Tj T* (those with a negative result. Reports of an increased relative risk rang\ e from 1.6 to 2.8 for nuchal translucency )Tj 0 -1.56 TD (measurements )Tj ET q 6.4121094 0 0 8.549469 190.6490479 491.8365784 cm /Im0 Do Q BT /T1_0 1 Tf 9.9744 0 0 9.9744 197.0612 491.8366 Tm (3mm and would diminish the detection rate of nuchal translucency measure\ ment.)Tj 0 0.314 0.627 rg 7.9795 0 0 7.9795 521.4582 496.9435 Tm (20)Tj 0 0 0 rg 1 -0.32 Td (,)Tj 0 0.314 0.627 rg 0.25 0.32 Td (21)Tj 0 0 0 rg 9.9744 0 0 9.9744 539.4121 491.8366 Tm ( In our )Tj -40.937 -1.2 Td (analysis, a relative risk of 2.8 would result in 1.3 more liveborn babie\ s with Down's syndrome per 10)Tj 40.667 0 Td (000 )Tj -40.667 -1.2 Td (pregnancies after measuring nuchal translucency, but the strategy would \ still be cost effective.)Tj 0 -2.557 TD (The choice of screening strategy may be affected by several factors that\ were beyond the scope of our analysis. )Tj 0 -1.56 TD (Firstly, we did not adopt a societal perspective,)Tj 0 0.314 0.627 rg 7.9795 0 0 7.9795 319.199 431.9367 Tm (13)Tj 0 0 0 rg 9.9744 0 0 9.9744 327.1785 426.8298 Tm ( which would seek to maximise health gain for a given cost. Such )Tj -19.659 -1.2 Td (analyses are problematic in terms of measures of effect\227for example, \ should the outcome measure be prevented )Tj T* (liveborn baby with Down's syndrome or quality adjusted life years.)Tj 0 0.314 0.627 rg 7.9795 0 0 7.9795 399.3931 404.4052 Tm (22)Tj 0 0 0 rg 9.9744 0 0 9.9744 407.3726 399.2983 Tm ( There are also difficult decisions about )Tj -27.699 -1.2 Td (which costs to include. Some previous cost effectiveness analyses includ\ ed direct and indirect lifetime incremental )Tj 0 -1.2 TD (costs per liveborn baby with Down's syndrome \(including education, heal\ th, and lost productivity\). These ranged )Tj 0 -1.56 TD (from \24385)Tj 3.908 0 Td (000 in 1990)Tj 0 0.314 0.627 rg 7.9795 0 0 7.9795 217.7324 364.9044 Tm (23)Tj 0 0 0 rg 9.9744 0 0 9.9744 225.7119 359.7975 Tm ( to \243340)Tj 3.492 0 Td (000 in 1996.)Tj 0 0.314 0.627 rg 7.9795 0 0 7.9795 310.6965 364.9044 Tm (24)Tj 0 0 0 rg 9.9744 0 0 9.9744 318.676 359.7975 Tm ( The studies avoided including other indirect costs attributable to )Tj -18.807 -1.2 Td (fetal losses by assuming a replacement pregnancy.)Tj 0 -2.557 TD (If the lowest estimate \(\24385)Tj 10.879 0 Td (000\) for the incremental lifetime costs associated with a Down's syndro\ me child is )Tj -10.879 -1.2 Td (included in our analysis the net saving compared with no screening would\ be largest for the integrated test. The net )Tj 0 -1.291 TD (saving would be \243548)Tj 9.019 0 Td (000 \(costs avoided \(9.7 Down's syndrome babies prevented \327 \24385)Tj 26.565 0 Td (000\))Tj /T1_2 1 Tf (-)Tj /T1_0 1 Tf (screening )Tj -35.585 -1.2 Td (programme costs \(\243276)Tj 9.657 0 Td (000\)\).)Tj /T1_1 1 Tf 11.9693 0 0 11.9693 131.092 258.2864 Tm (Factors that could affect results)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 131.092 245.6367 Tm (Three factors that we did not consider may affect our results. Firstly, \ capital costs for additional laboratory or )Tj 0 -1.2 TD (clinical capacity may be incurred for use of the enzyme linked immunosor\ bent assay \(ELISA\) test for inhibin A )Tj T* (\(the fourth serum marker in the quadruple test\), implementation of rou\ tine nuchal translucency measurement, or )Tj T* (the creation of additional facilities for chorionic villus sampling. Sec\ ondly, uptake of all screening tests and )Tj T* (termination may not be the same for all strategies and may be lower for \ the integrated test, which requires two )Tj T* (visits. Decreased uptake of termination in later pregnancy is likely and\ would mean that our analysis overestimates )Tj 0 -1.2 TD (the effectiveness of the integrated and quadruple tests. Thirdly, servic\ e providers need to provide for women who )Tj 0 -1.2 TD (attend antenatal booking clinic after the first trimester \(up to 35% ba\ sed on results from 21)Tj 36.514 0 Td (000 women in six inner )Tj -36.514 -1.56 Td (London maternity units)Tj 0 0.314 0.627 rg 7.9795 0 0 7.9795 224.7415 151.3964 Tm (25)Tj 0 0 0 rg 9.9744 0 0 9.9744 232.721 146.2896 Tm (\). Alternative strategies for late attenders include no screening, the \ quadruple test, or )Tj -10.189 -1.2 Td (strategies to encourage earlier attendance at antenatal booking clinic\227\ for example, by speeding up referrals from )Tj T* (primary care. )Tj /T1_1 1 Tf 11.9693 0 0 11.9693 131.092 95.1317 Tm (Conclusions)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 131.092 82.4819 Tm (The choice of screening strategy should be between the integrated test, \ first trimester combined test, quadruple )Tj T* (test, or nuchal translucency measurement. Screening based on maternal ag\ e, the second trimester double test, and )Tj T* (the first trimester serum test would be less effective, less safe, and m\ ore costly than these four options. )Tj ET EMC /Artifact <>BDC Q 0 0 0 rg BT /T1_0 1 Tf 6.4121 0 0 6.4121 18 9.1339 Tm (http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=37550 \(5 of 9\ \)8.2.2007 11:14:34)Tj ET EMC endstream endobj 399 0 obj<>stream /Artifact <>BDC 0 0 0 rg 0 i BT /T1_0 1 Tf 0 Tc 0 Tw 0 Ts 100 Tz 0 Tr 6.4121 0 0 6.4121 18 782.1339 Tm (Screening for Down's syndrome: effects, safety, and cost effectiveness o\ f first and second trimester strategies)Tj ET EMC /WebCaptureBG BMC /WebCaptureFN <>BDC q 0 18 612 756 re W* n /Artifact <>BDC Q 0.973 0.973 0.973 rg 7.125 18 604.875 756 re f EMC q 0 18 612 756 re W* n /Artifact <>BDC Q 0 0.467 0.667 rg 9.262 765.87 m 112.568 765.87 l 112.568 765.157 l 9.262 765.157 l h f EMC q 0 18 612 756 re W* n /Artifact <>BDC Q q 18.524 751.62 94.044 13.537 re W* n 0.753 0.753 0.753 RG 0.712 w 10 M 0 j 1 J [0 1.425]0.713 d 18.524 751.977 m 112.568 751.977 l S EMC Q q 0 18 612 756 re W* n /Artifact <>BDC Q q 18.524 738.084 94.044 13.537 re W* n 0.753 0.753 0.753 RG 0.712 w 10 M 0 j 1 J [0 1.425]0.713 d 18.524 738.44 m 112.568 738.44 l S EMC Q q 0 18 612 756 re W* n /Artifact <>BDC Q q 18.524 724.547 94.044 13.537 re W* n 0.753 0.753 0.753 RG 0.712 w 10 M 0 j 1 J [0 1.425]0.713 d 18.524 724.903 m 112.568 724.903 l S EMC Q q 0 18 612 756 re W* n /Artifact <>BDC Q q 18.524 711.01 94.044 13.537 re W* n 0.753 0.753 0.753 RG 0.712 w 10 M 0 j 1 J [0 1.425]0.713 d 18.524 711.367 m 112.568 711.367 l S EMC Q q 0 18 612 756 re W* n /Artifact <>BDC Q q 18.524 697.474 94.044 13.537 re W* n 0.753 0.753 0.753 RG 0.712 w 10 M 0 j 1 J [0 1.425]0.713 d 18.524 697.83 m 112.568 697.83 l S EMC Q q 0 18 612 756 re W* n /Artifact <>BDC Q q 18.524 683.937 94.044 13.537 re W* n 0.753 0.753 0.753 RG 0.712 w 10 M 0 j 1 J [0 1.425]0.713 d 18.524 684.293 m 112.568 684.293 l S EMC Q q 0 18 612 756 re W* n /Artifact <>BDC Q q 11.399 661.495 101.169 22.442 re W* n 0.753 0.753 0.753 RG 0.712 w 10 M 0 j 1 J [0 1.425]0.713 d 11.399 661.851 m 112.568 661.851 l S EMC Q q 0 18 612 756 re W* n /Artifact <>BDC Q q 18.524 647.958 94.044 13.537 re W* n 0.753 0.753 0.753 RG 0.712 w 10 M 0 j 1 J [0 1.425]0.713 d 18.524 648.314 m 112.568 648.314 l S EMC Q q 0 18 612 756 re W* n /Artifact <>BDC Q q 18.524 634.421 94.044 13.537 re W* n 0.753 0.753 0.753 RG 0.712 w 10 M 0 j 1 J [0 1.425]0.713 d 18.524 634.778 m 112.568 634.778 l S EMC Q q 0 18 612 756 re W* n /Artifact <>BDC Q 0 0.447 0.659 rg 131.983 749.319 463.097 15.66 re f 131.092 765.87 m 595.97 765.87 l 595.079 764.979 l 131.983 764.979 l h f 131.092 765.87 m 131.092 748.429 l 131.983 749.319 l 131.983 764.979 l h f 595.97 765.87 m 595.97 748.429 l 595.079 749.319 l 595.079 764.979 l h f 131.092 748.429 m 595.97 748.429 l 595.079 749.319 l 131.983 749.319 l h f EMC q 0 18 612 756 re W* n /Artifact <>BDC Q 0.973 0.973 0.973 rg 131.092 69.103 m 164.577 69.103 l 163.865 68.391 l 131.804 68.391 l h f 131.092 69.103 m 131.092 58.103 l 131.804 58.816 l 131.804 68.391 l h f 164.577 69.103 m 164.577 58.103 l 163.865 58.816 l 163.865 68.391 l h f 131.092 58.103 m 164.577 58.103 l 163.865 58.816 l 131.804 58.816 l h f EMC q 0 18 612 756 re W* n /Artifact <>BDC Q 131.092 38.382 m 164.577 38.382 l 163.865 37.67 l 131.804 37.67 l h f 131.092 38.382 m 131.092 30.824 l 131.804 30.824 l 131.804 37.67 l h f 164.577 38.382 m 164.577 30.824 l 163.865 30.824 l 163.865 37.67 l h f EMC q 0 18 612 756 re W* n /Artifact <>BDC Q /CS0 cs /P0 scn 114.705 30.824 14.249 737.476 re f EMC EMC EMC /Article <>BDC q 0 18 612 756 re W* n 0 0.251 0.502 rg BT /TT0 1 Tf 7.4808 0 0 7.4808 22.0862 757.5877 Tm (Top)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 34.9756 757.5877 Tm ( )Tj /TT0 1 Tf 7.4808 0 0 7.4808 22.0862 744.051 Tm (Abstract)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 49.5257 744.051 Tm ( )Tj /TT0 1 Tf 7.4808 0 0 7.4808 22.0862 730.5144 Tm (Introduction)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 61.1733 730.5144 Tm ( )Tj /TT0 1 Tf 7.4808 0 0 7.4808 22.0862 716.9777 Tm (Methods)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 50.775 716.9777 Tm ( )Tj /TT0 1 Tf 7.4808 0 0 7.4808 22.0862 703.441 Tm (Results)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 47.0271 703.441 Tm ( )Tj /TT0 1 Tf 7.4808 0 0 7.4808 22.0862 689.9044 Tm (Discussion)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 58.2483 689.9044 Tm ( )Tj ET q 3.5622864 0 0 7.1245575 14.9615784 675.9219971 cm /Im0 Do Q 0.502 0.502 0.502 rg BT /TT0 1 Tf 7.4808 0 0 7.4808 18.5239 678.283 Tm (Commentary: Results may )Tj -0.476 -1.447 Td (not be widely applicable)Tj 0 0 1 rg /T1_0 1 Tf 9.9744 0 0 9.9744 94.3777 667.462 Tm ( )Tj 0 0.251 0.502 rg /TT0 1 Tf 7.4808 0 0 7.4808 22.0862 653.9253 Tm (Authors' response)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 82.1419 653.9253 Tm ( )Tj /TT0 1 Tf 7.4808 0 0 7.4808 22.0862 640.3886 Tm (References)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 60.3354 640.3886 Tm ( )Tj 1 1 1 rg /TT1 1 Tf 10.9718 0 0 10.9718 205.7889 753.5524 Tm (Commentary: Results may not be widely applicable)Tj 0 0 0 rg /T1_0 1 Tf 9.9744 0 0 9.9744 131.092 726.3251 Tm (Wallace, Euan M;Mulvey, Sheila \(Centre for Women's Health Research, Dep\ artment of Obstetrics and )Tj 0 -1.2 TD (Gynaecology, Monash University, Monash Medical Centre, Clayton, Victoria\ 3168, Australia\). )Tj 0 -2.557 TD (The average age at which women in Western countries choose to have child\ ren continues to increase. Although )Tj 0 -1.2 TD (this trend has several important implications for the outcome of pregnan\ cy, one of the most obvious effects is an )Tj 0 -1.56 TD (increase in the incidence of Down's syndrome.)Tj 0 0.314 0.627 rg 7.9795 0 0 7.9795 317.0944 666.4253 Tm (1-1)Tj 0 0 0 rg 9.9744 0 0 9.9744 327.7311 661.3184 Tm ( Prenatal screening for Down's syndrome has become an )Tj -19.714 -1.2 Td (established part of antenatal care in many centres, resulting in a reduc\ tion in the number of babies born with )Tj T* (Down's syndrome in the populations screened.)Tj 0 0.314 0.627 rg 7.9795 0 0 7.9795 316.835 638.8938 Tm (1-1)Tj 0 0 0 rg 9.9744 0 0 9.9744 131.092 608.2809 Tm (Several serum markers of Down's syndrome have been described, and differ\ ent screening programmes use )Tj T* (different combinations of markers, making it difficult to compare their \ results.)Tj 0 0.314 0.627 rg 7.9795 0 0 7.9795 443.5796 597.8255 Tm (1-2)Tj 0 0 0 rg 9.9744 0 0 9.9744 454.2163 592.7187 Tm ( The recent introduction of first )Tj -32.395 -1.2 Td (trimester serum and ultrasound screening has further complicated such co\ mparisons. Therefore, it is often unclear )Tj 0 -1.2 TD (which screening strategy is the most effective, the most cost effective,\ or the most appropriate for a given setting. )Tj T* (Gilbert and her colleagues summarise various approaches to screening and\ describe the most cost effective )Tj T* (strategies. Such information will be invaluable to all those providing a\ ntenatal care.)Tj /T1_1 1 Tf 11.9693 0 0 11.9693 131.092 517.6223 Tm (Limitations)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 131.092 504.9725 Tm (Some authorities are likely to disagree with the conclusions reached by \ Gilbert et al. There is evidence that simple )Tj 0 -1.291 TD (two marker protocols \(such as )Tj /T1_2 1 Tf (a)Tj /T1_0 1 Tf ( fetoprotein and free \337 human chorionic gonadotrophin\) can achieve h\ igher )Tj 0 -1.2 TD (detection rates than those estimated by Gilbert et al for more complex c\ ombinations, even after correction for the )Tj 0 -1.56 TD (high rate of spontaneous loss of pregnancies affected by Down's syndrome\ .)Tj 0 0.314 0.627 rg 7.9795 0 0 7.9795 431.7799 469.6698 Tm (1-2)Tj 0 0 0 rg 1.333 -0.32 Td (,)Tj 0 0.314 0.627 rg 0.25 0.32 Td (1-3)Tj 0 0 0 rg 9.9744 0 0 9.9744 455.0481 464.563 Tm ( How can this be? )Tj -32.479 -2.557 Td (A potential limitation of the analyses is that the effectiveness modelli\ ng is based on an archived set of serum )Tj 0 -1.2 TD (samples derived from 77 women with pregnancies affected by Down's syndro\ me and 385 with unaffected )Tj T* (pregnancies, rather than an analysis of published detection rates from p\ rospective series, as was done for nuchal )Tj T* (translucency. If the archived data set differs from the population being\ screened then the performance )Tj T* (characteristics may not be the same in practice. This emphasises the imp\ ortance of evaluating screening tests )Tj T* (locally, where the expertise exists, rather than relying on a single arc\ hived serum bank.)Tj 0 -2.557 TD (It is also possible that marker combinations not analysed in this report\ will offer highly effective screening. For )Tj 0 -1.56 TD (example, second trimester serum screening has better detection rates tha\ n first trimester tests.)Tj 0 0.314 0.627 rg 7.9795 0 0 7.9795 503.396 343.2494 Tm (1-4)Tj 0 0 0 rg 9.9744 0 0 9.9744 514.0327 338.1425 Tm ( The combination )Tj -38.392 -1.2 Td (of nuchal translucency with second trimester serum markers may prove mor\ e effective than the first trimester test )Tj 0 -1.2 TD (that Gilbert et al recommend. Several prospective comparative studies ar\ e underway worldwide that will )Tj T* (investigate this possibility.)Tj 0 -2.557 TD (The cost comparisons of the various strategies highlight that more expen\ sive approaches may be the most cost )Tj 0 -1.2 TD (effective. Such insights will be extremely helpful to health planners. H\ owever, the costings used in the analyses are )Tj T* (for a programme within a large public service such as the NHS and will n\ ot easily translate across healthcare )Tj T* (systems. For example, the \2434.40 allowed for measuring nuchal transluc\ ency is much less than the $200 \(\243143\) )Tj 0 -1.56 TD (estimated in the United States.)Tj 0 0.314 0.627 rg 7.9795 0 0 7.9795 252.7197 230.3656 Tm (1-5)Tj 0 0 0 rg 9.9744 0 0 9.9744 263.3564 225.2587 Tm ( Again, it will be important for local programmes to derive local costs \ before )Tj -13.26 -1.2 Td (planning their service.)Tj /T1_1 1 Tf 11.9693 0 0 11.9693 131.092 186.0701 Tm (Women's views)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 131.092 173.4204 Tm (What is not covered by these analyses, although the authors mention it, \ is patient preference. We have little )Tj 0 -1.2 TD (information about what women prefer in screening, but there is some evid\ ence that they want testing as early in )Tj 0 -1.56 TD (pregnancy as possible, even if a later test performs slightly better.)Tj 0 0.314 0.627 rg 7.9795 0 0 7.9795 393.1491 150.9957 Tm (1-6)Tj 0 0 0 rg 9.9744 0 0 9.9744 403.7858 145.8888 Tm ( Such information is surely fundamental to the )Tj -27.339 -1.2 Td (development of future screening programmes. It would be unfortunate if t\ he technical advances in screening were )Tj 0 -1.2 TD (assessed and compared without considering women's wishes. Similarly, it \ is unacceptable that access to screening )Tj T* (for Down's syndrome varies across the United Kingdom. Contributions such\ as that by Gilbert et al will inform )Tj T* (relevant authorities, such as the UK National Screening Committee, and h\ elp ensure that appropriate and high )Tj T* (quality screening is available to all women who want it. )Tj 7.9795 0 0 7.9795 151.2334 61.5375 Tm (1-1.)Tj 2.387 0.089 Td (Cheffins T, Chan A, Haan EA, Ranieri E, Ryall RG, Keane RJ, et al. The i\ mpact of maternal serum screening on the birth )Tj T* (prevalence of Down's syndrome and the use of amniocentesis and chorionic\ villus sampling in South )Tj T* (Australia. )Tj /T1_3 1 Tf (Br J Obstet Gynaecol. )Tj /T1_0 1 Tf (2000;107:1453\2261459.)Tj ET EMC /Artifact <>BDC Q 0 0 0 rg BT /T1_0 1 Tf 6.4121 0 0 6.4121 18 9.1339 Tm (http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=37550 \(6 of 9\ \)8.2.2007 11:14:34)Tj ET EMC endstream endobj 400 0 obj<>stream /Artifact <>BDC 0 0 0 rg 0 i BT /T1_0 1 Tf 0 Tc 0 Tw 0 Ts 100 Tz 0 Tr 6.4121 0 0 6.4121 18 782.1339 Tm (Screening for Down's syndrome: effects, safety, and cost effectiveness o\ f first and second trimester strategies)Tj ET EMC /WebCaptureBG BMC /WebCaptureFN <>BDC q 0 18 612 756 re W* n /Artifact <>BDC Q 0.973 0.973 0.973 rg 7.125 18 604.875 756 re f EMC q 0 18 612 756 re W* n /Artifact <>BDC Q 131.092 768.3 m 131.092 758.012 l 131.804 758.725 l 131.804 768.3 l h f 164.577 768.3 m 164.577 758.012 l 163.865 758.725 l 163.865 768.3 l h f 131.092 758.012 m 164.577 758.012 l 163.865 758.725 l 131.804 758.725 l h f EMC q 0 18 612 756 re W* n /Artifact <>BDC Q 131.092 745.73 m 164.577 745.73 l 163.865 745.017 l 131.804 745.017 l h f 131.092 745.73 m 131.092 734.729 l 131.804 735.442 l 131.804 745.017 l h f 164.577 745.73 m 164.577 734.729 l 163.865 735.442 l 163.865 745.017 l h f 131.092 734.729 m 164.577 734.729 l 163.865 735.442 l 131.804 735.442 l h f EMC q 0 18 612 756 re W* n /Artifact <>BDC Q 131.092 723.159 m 164.577 723.159 l 163.865 722.447 l 131.804 722.447 l h f 131.092 723.159 m 131.092 712.159 l 131.804 712.871 l 131.804 722.447 l h f 164.577 723.159 m 164.577 712.159 l 163.865 712.871 l 163.865 722.447 l h f 131.092 712.159 m 164.577 712.159 l 163.865 712.871 l 131.804 712.871 l h f EMC q 0 18 612 756 re W* n /Artifact <>BDC Q 131.092 700.589 m 164.577 700.589 l 163.865 699.876 l 131.804 699.876 l h f 131.092 700.589 m 131.092 689.588 l 131.804 690.301 l 131.804 699.876 l h f 164.577 700.589 m 164.577 689.588 l 163.865 690.301 l 163.865 699.876 l h f 131.092 689.588 m 164.577 689.588 l 163.865 690.301 l 131.804 690.301 l h f EMC q 0 18 612 756 re W* n /Artifact <>BDC Q 131.092 678.018 m 164.577 678.018 l 163.865 677.305 l 131.804 677.305 l h f 131.092 678.018 m 131.092 667.018 l 131.804 667.73 l 131.804 677.305 l h f 164.577 678.018 m 164.577 667.018 l 163.865 667.73 l 163.865 677.305 l h f 131.092 667.018 m 164.577 667.018 l 163.865 667.73 l 131.804 667.73 l h f EMC q 0 18 612 756 re W* n /Artifact <>BDC Q 0 0.467 0.667 rg 9.262 624.491 m 112.568 624.491 l 112.568 623.779 l 9.262 623.779 l h f EMC q 0 18 612 756 re W* n /Artifact <>BDC Q q 18.524 610.242 94.044 13.537 re W* n 0.753 0.753 0.753 RG 0.712 w 10 M 0 j 1 J [0 1.425]0.713 d 18.524 610.598 m 112.568 610.598 l S EMC Q q 0 18 612 756 re W* n /Artifact <>BDC Q q 18.524 596.705 94.044 13.537 re W* n 0.753 0.753 0.753 RG 0.712 w 10 M 0 j 1 J [0 1.425]0.713 d 18.524 597.061 m 112.568 597.061 l S EMC Q q 0 18 612 756 re W* n /Artifact <>BDC Q q 18.524 583.169 94.044 13.537 re W* n 0.753 0.753 0.753 RG 0.712 w 10 M 0 j 1 J [0 1.425]0.713 d 18.524 583.525 m 112.568 583.525 l S EMC Q q 0 18 612 756 re W* n /Artifact <>BDC Q q 18.524 569.632 94.044 13.537 re W* n 0.753 0.753 0.753 RG 0.712 w 10 M 0 j 1 J [0 1.425]0.713 d 18.524 569.988 m 112.568 569.988 l S EMC Q q 0 18 612 756 re W* n /Artifact <>BDC Q q 18.524 556.095 94.044 13.537 re W* n 0.753 0.753 0.753 RG 0.712 w 10 M 0 j 1 J [0 1.425]0.713 d 18.524 556.451 m 112.568 556.451 l S EMC Q q 0 18 612 756 re W* n /Artifact <>BDC Q q 18.524 542.559 94.044 13.537 re W* n 0.753 0.753 0.753 RG 0.712 w 10 M 0 j 1 J [0 1.425]0.713 d 18.524 542.915 m 112.568 542.915 l S EMC Q q 0 18 612 756 re W* n /Artifact <>BDC Q q 18.524 520.116 94.044 22.442 re W* n 0.753 0.753 0.753 RG 0.712 w 10 M 0 j 1 J [0 1.425]0.713 d 18.524 520.472 m 112.568 520.472 l S EMC Q q 0 18 612 756 re W* n /Artifact <>BDC Q q 11.399 506.58 101.169 13.537 re W* n 0.753 0.753 0.753 RG 0.712 w 10 M 0 j 1 J [0 1.425]0.713 d 11.399 506.936 m 112.568 506.936 l S EMC Q q 0 18 612 756 re W* n /Artifact <>BDC Q q 18.524 493.043 94.044 13.537 re W* n 0.753 0.753 0.753 RG 0.712 w 10 M 0 j 1 J [0 1.425]0.713 d 18.524 493.399 m 112.568 493.399 l S EMC Q q 0 18 612 756 re W* n /Artifact <>BDC Q 0 0.447 0.659 rg 131.983 607.941 463.097 15.66 re f 131.092 624.491 m 595.97 624.491 l 595.079 623.6 l 131.983 623.6 l h f 131.092 624.491 m 131.092 607.05 l 131.983 607.941 l 131.983 623.6 l h f 595.97 624.491 m 595.97 607.05 l 595.079 607.941 l 595.079 623.6 l h f 131.092 607.05 m 595.97 607.05 l 595.079 607.941 l 131.983 607.941 l h f EMC q 0 18 612 756 re W* n /Artifact <>BDC Q 0.973 0.973 0.973 rg 131.092 456.691 m 164.577 456.691 l 163.865 455.979 l 131.804 455.979 l h f 131.092 456.691 m 131.092 445.691 l 131.804 446.403 l 131.804 455.979 l h f 164.577 456.691 m 164.577 445.691 l 163.865 446.403 l 163.865 455.979 l h f 131.092 445.691 m 164.577 445.691 l 163.865 446.403 l 131.804 446.403 l h f EMC q 0 18 612 756 re W* n /Artifact <>BDC Q 0 0.447 0.659 rg 131.983 386.614 463.097 15.66 re f 131.092 403.164 m 595.97 403.164 l 595.079 402.274 l 131.983 402.274 l h f 131.092 403.164 m 131.092 385.723 l 131.983 386.614 l 131.983 402.274 l h f 595.97 403.164 m 595.97 385.723 l 595.079 386.614 l 595.079 402.274 l h f 131.092 385.723 m 595.97 385.723 l 595.079 386.614 l 131.983 386.614 l h f EMC q 0 18 612 756 re W* n /Artifact <>BDC Q 131.983 261.913 463.097 15.66 re f 131.092 278.463 m 595.97 278.463 l 595.079 277.572 l 131.983 277.572 l h f 131.092 278.463 m 131.092 261.022 l 131.983 261.913 l 131.983 277.572 l h f 595.97 278.463 m 595.97 261.022 l 595.079 261.913 l 595.079 277.572 l h f 131.092 261.022 m 595.97 261.022 l 595.079 261.913 l 131.983 261.913 l h f EMC q 0 18 612 756 re W* n /Artifact <>BDC Q /CS0 cs /P0 scn 114.705 30.824 14.249 737.476 re f EMC EMC EMC /Article <>BDC q 0 18 612 756 re W* n 0 0 0 rg BT /T1_0 1 Tf 7.9795 0 0 7.9795 151.2334 761.4468 Tm (1-2.)Tj 2.387 0 Td (Wald NJ, Kennard A, Hackshaw A, McGuire A. Antenatal screening for Down'\ s syndrome. )Tj /T1_1 1 Tf (J Med Screen. )Tj /T1_0 1 Tf (1997;4:181\226246. )Tj 0 -1.2 TD ([)Tj ET 0 0.314 0.627 RG 0.402 w 10 M 0 j 0 J []0 d 172.934 750.665 m 199.977 750.665 l S 0 0.314 0.627 rg BT /T1_0 1 Tf 7.9795 0 0 7.9795 172.9342 751.8714 Tm (PubMed)Tj 0 0 0 rg (])Tj -2.72 -1.718 Td (1-3.)Tj 2.387 0.089 Td (Spencer K. Second trimester prenatal screening for Down's syndrome using\ alpha-fetoprotein and free beta hCG: a seven year )Tj T* (review. )Tj /T1_1 1 Tf (Br J Obstet Gynaecol. )Tj /T1_0 1 Tf (1999;106:1287\2261293. [)Tj ET 343.807 728.094 m 370.85 728.094 l S 0 0.314 0.627 rg BT /T1_0 1 Tf 7.9795 0 0 7.9795 343.8075 729.3008 Tm (PubMed)Tj 0 0 0 rg (])Tj -24.134 -1.718 Td (1-4.)Tj 2.387 0.089 Td (Berry E, Aitken DA, Crossley JA, Macri JN, Connor JM. Screening for Down\ 's syndrome: changes in marker levels and detection )Tj T* (rates between first and second trimesters. )Tj /T1_1 1 Tf (Br J Obstet Gynaecol. )Tj /T1_0 1 Tf (1997;104:811\226817. [)Tj ET 443.751 705.524 m 470.793 705.524 l S 0 0.314 0.627 rg BT /T1_0 1 Tf 7.9795 0 0 7.9795 443.7509 706.7302 Tm (PubMed)Tj 0 0 0 rg (])Tj -36.659 -1.718 Td (1-5.)Tj 2.387 0.089 Td (Vintzileos AM, Ananth CV, Smulian JC, Day-Salvatore DL, Beazoglou T, Knu\ ppel RA. Cost-benefit analysis of prenatal diagnosis )Tj T* (for Down syndrome using the British or the American approach. )Tj /T1_1 1 Tf (Obstet Gynecol. )Tj /T1_0 1 Tf (2000;95:577\226583. [)Tj ET 494.732 682.953 m 521.775 682.953 l S 0 0.314 0.627 rg BT /T1_0 1 Tf 7.9795 0 0 7.9795 494.732 684.1596 Tm (PubMed)Tj 0 0 0 rg (])Tj -43.048 -1.718 Td (1-6.)Tj 2.387 0.089 Td (Mulvey S, Wallace EM. Women's knowledge of and attitudes to first and se\ cond trimester screening for Down's )Tj T* (syndrome. )Tj /T1_1 1 Tf (Br J Obstet Gynaecol. )Tj /T1_0 1 Tf (2000;107:1302\2261305.)Tj 0 0.251 0.502 rg /TT0 1 Tf 7.4808 0 0 7.4808 22.0862 616.2091 Tm (Top)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 34.9756 616.2091 Tm ( )Tj /TT0 1 Tf 7.4808 0 0 7.4808 22.0862 602.6725 Tm (Abstract)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 49.5257 602.6725 Tm ( )Tj /TT0 1 Tf 7.4808 0 0 7.4808 22.0862 589.1358 Tm (Introduction)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 61.1733 589.1358 Tm ( )Tj /TT0 1 Tf 7.4808 0 0 7.4808 22.0862 575.5991 Tm (Methods)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 50.775 575.5991 Tm ( )Tj /TT0 1 Tf 7.4808 0 0 7.4808 22.0862 562.0624 Tm (Results)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 47.0271 562.0624 Tm ( )Tj /TT0 1 Tf 7.4808 0 0 7.4808 22.0862 548.5258 Tm (Discussion)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 58.2483 548.5258 Tm ( )Tj /TT0 1 Tf 7.4808 0 0 7.4808 22.0862 536.9044 Tm (Commentary: Results may )Tj 0 -1.447 TD (not be widely applicable)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 101.5022 526.0834 Tm ( )Tj ET q 3.5622864 0 0 7.1245575 14.9615784 510.854248 cm /Im0 Do Q 0.502 0.502 0.502 rg BT /TT0 1 Tf 7.4808 0 0 7.4808 18.5239 512.5467 Tm (Authors' response)Tj 0 0 1 rg /T1_0 1 Tf 9.9744 0 0 9.9744 78.5797 512.5467 Tm ( )Tj 0 0.251 0.502 rg /TT0 1 Tf 7.4808 0 0 7.4808 22.0862 499.0101 Tm (References)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 60.3354 499.0101 Tm ( )Tj 1 1 1 rg /TT1 1 Tf 10.9718 0 0 10.9718 307.4868 612.1738 Tm (Authors' response)Tj 0 0 0 rg /T1_0 1 Tf 9.9744 0 0 9.9744 131.092 584.9465 Tm (Wallace and Mulvey criticise our study for relying on a single archived \ serum bank. Instead, they advocate )Tj 0 -1.2 TD (comparing detection rates from \223prospective studies,\224 by which the\ y mean routinely collected hospital data. We )Tj T* (disagree. It is well known that data from routine practice may overestim\ ate the performance of screen tests because )Tj T* (positive results lead to interventions whereas affected pregnancies with\ negative results may not be counted )Tj 0 -1.56 TD (\(termed verification bias\).)Tj 0 0.314 0.627 rg 7.9795 0 0 7.9795 234.9653 538.5834 Tm (2-1)Tj 0 0 0 rg 9.9744 0 0 9.9744 245.6019 533.4765 Tm ( Such bias depends on the gestational age at testing and can be allowed \ for only )Tj -11.48 -1.2 Td (indirectly. Differences in detection rates \(assuming a constant false p\ ositive rate\) may also relate to uptake of )Tj 0 -1.2 TD (interventions and referral patterns. Finally, we required the test perfo\ rmance characteristics rather than the )Tj T* (detection rate in order to standardise for age and cut-off point for pos\ itivity. The study based on an archived serum )Tj T* (bank avoided biased detection of affected fetuses \(all were karyotyped\)\ , took account of ultrasound pregnancy )Tj T* (dating, and reported performance characteristics for all the serum tests\ .)Tj 7.9795 0 0 7.9795 151.2334 449.1251 Tm (2-1.)Tj 2.387 0.089 Td (Mol BW, Lijmer JG, van der Meulen J, Pajkrt E, Bilardo CM, Bossuyt PM. E\ ffect of study design on the association between )Tj T* (nuchal translucency measurement and Down syndrome. )Tj /T1_1 1 Tf (Gynecol. )Tj /T1_0 1 Tf (1999;94:864\226869.)Tj 9.9744 0 0 9.9744 9.2619 394.5974 Tm ( )Tj 1 1 1 rg /TT1 1 Tf 10.9718 0 0 10.9718 307.0259 390.8471 Tm (Acknowledgments)Tj 0 0 0 rg /T1_0 1 Tf 9.9744 0 0 9.9744 131.092 363.6198 Tm (John Kingdom and Susan Bewley provided advice on the development of the \ project and commented on drafts of )Tj T* (the report. Maureen Dalziel chaired the reference group and commented on\ the study design. Roxanne )Tj T* (Chamberlain, Jean Chapple, Nick Fisk, Mike Gill, David Highton, M L Ko, \ Mike Lobb, Lucy Moore, Tracey )Tj T* (Reeves, and Tracy Stein were members of the reference group and commente\ d on the study design and results. )Tj T* (Susan Bewley, Elizabeth Dormandy, Ross Hastings, Wayne Huttly, Linda Mul\ hair, Kypros Nicolaides, and Pran )Tj T* (Pandya provided information on screening practices. The report may not r\ eflect the views of the funding body.)Tj -12.214 -3.396 Td ( )Tj 1 1 1 rg /TT1 1 Tf 10.9718 0 0 10.9718 332.8536 266.1458 Tm (Footnotes)Tj 0 0 0 rg /T1_0 1 Tf 8.4782 0 0 8.4782 131.092 240.2036 Tm (Funding: The project was commissioned by Maureen Dalziel, Sally Davies, \ and Ron Kerr from the London regional office of the NHS )Tj T* (Executive.)Tj 0 -2.797 TD (Competing interests: None declared.)Tj 1.008 -2.797 Td ( Competing interests: EMW holds the patent for use of inhibin A as a mar\ ker of Down's syndrome.)Tj ET EMC /Artifact <>BDC Q 0 0 0 rg BT /T1_0 1 Tf 6.4121 0 0 6.4121 18 9.1339 Tm (http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=37550 \(7 of 9\ \)8.2.2007 11:14:34)Tj ET EMC endstream endobj 401 0 obj<>stream /Artifact <>BDC 0 0 0 rg 0 i BT /T1_0 1 Tf 0 Tc 0 Tw 0 Ts 100 Tz 0 Tr 6.4121 0 0 6.4121 18 782.1339 Tm (Screening for Down's syndrome: effects, safety, and cost effectiveness o\ f first and second trimester strategies)Tj ET EMC /WebCaptureBG BMC /WebCaptureFN <>BDC q 0 18 612 756 re W* n /Artifact <>BDC Q 0.973 0.973 0.973 rg 7.125 18 604.875 756 re f EMC q 0 18 612 756 re W* n /Artifact <>BDC Q 0 0.467 0.667 rg 9.262 766.037 m 112.568 766.037 l 112.568 765.325 l 9.262 765.325 l h f EMC q 0 18 612 756 re W* n /Artifact <>BDC Q q 18.524 751.788 94.044 13.537 re W* n 0.753 0.753 0.753 RG 0.712 w 10 M 0 j 1 J [0 1.425]0.713 d 18.524 752.144 m 112.568 752.144 l S EMC Q q 0 18 612 756 re W* n /Artifact <>BDC Q q 18.524 738.251 94.044 13.537 re W* n 0.753 0.753 0.753 RG 0.712 w 10 M 0 j 1 J [0 1.425]0.713 d 18.524 738.608 m 112.568 738.608 l S EMC Q q 0 18 612 756 re W* n /Artifact <>BDC Q q 18.524 724.715 94.044 13.537 re W* n 0.753 0.753 0.753 RG 0.712 w 10 M 0 j 1 J [0 1.425]0.713 d 18.524 725.071 m 112.568 725.071 l S EMC Q q 0 18 612 756 re W* n /Artifact <>BDC Q q 18.524 711.178 94.044 13.537 re W* n 0.753 0.753 0.753 RG 0.712 w 10 M 0 j 1 J [0 1.425]0.713 d 18.524 711.534 m 112.568 711.534 l S EMC Q q 0 18 612 756 re W* n /Artifact <>BDC Q q 18.524 697.641 94.044 13.537 re W* n 0.753 0.753 0.753 RG 0.712 w 10 M 0 j 1 J [0 1.425]0.713 d 18.524 697.998 m 112.568 697.998 l S EMC Q q 0 18 612 756 re W* n /Artifact <>BDC Q q 18.524 684.105 94.044 13.537 re W* n 0.753 0.753 0.753 RG 0.712 w 10 M 0 j 1 J [0 1.425]0.713 d 18.524 684.461 m 112.568 684.461 l S EMC Q q 0 18 612 756 re W* n /Artifact <>BDC Q q 18.524 661.662 94.044 22.442 re W* n 0.753 0.753 0.753 RG 0.712 w 10 M 0 j 1 J [0 1.425]0.713 d 18.524 662.019 m 112.568 662.019 l S EMC Q q 0 18 612 756 re W* n /Artifact <>BDC Q q 18.524 648.126 94.044 13.537 re W* n 0.753 0.753 0.753 RG 0.712 w 10 M 0 j 1 J [0 1.425]0.713 d 18.524 648.482 m 112.568 648.482 l S EMC Q q 0 18 612 756 re W* n /Artifact <>BDC Q q 11.399 634.589 101.169 13.537 re W* n 0.753 0.753 0.753 RG 0.712 w 10 M 0 j 1 J [0 1.425]0.713 d 11.399 634.945 m 112.568 634.945 l S EMC Q q 0 18 612 756 re W* n /Artifact <>BDC Q 0 0.447 0.659 rg 131.983 749.487 463.097 15.66 re f 131.092 766.037 m 595.97 766.037 l 595.079 765.147 l 131.983 765.147 l h f 131.092 766.037 m 131.092 748.596 l 131.983 749.487 l 131.983 765.147 l h f 595.97 766.037 m 595.97 748.596 l 595.079 749.487 l 595.079 765.147 l h f 131.092 748.596 m 595.97 748.596 l 595.079 749.487 l 131.983 749.487 l h f EMC q 0 18 612 756 re W* n /Artifact <>BDC Q 0.973 0.973 0.973 rg 131.092 742.362 m 164.577 742.362 l 163.865 741.65 l 131.804 741.65 l h f 131.092 742.362 m 131.092 731.362 l 131.804 732.074 l 131.804 741.65 l h f 164.577 742.362 m 164.577 731.362 l 163.865 732.074 l 163.865 741.65 l h f 131.092 731.362 m 164.577 731.362 l 163.865 732.074 l 131.804 732.074 l h f EMC q 0 18 612 756 re W* n /Artifact <>BDC Q 131.092 719.792 m 164.577 719.792 l 163.865 719.079 l 131.804 719.079 l h f 131.092 719.792 m 131.092 708.791 l 131.804 709.504 l 131.804 719.079 l h f 164.577 719.792 m 164.577 708.791 l 163.865 709.504 l 163.865 719.079 l h f 131.092 708.791 m 164.577 708.791 l 163.865 709.504 l 131.804 709.504 l h f EMC q 0 18 612 756 re W* n /Artifact <>BDC Q 131.092 706.797 m 164.577 706.797 l 163.865 706.084 l 131.804 706.084 l h f 131.092 706.797 m 131.092 695.796 l 131.804 696.509 l 131.804 706.084 l h f 164.577 706.797 m 164.577 695.796 l 163.865 696.509 l 163.865 706.084 l h f 131.092 695.796 m 164.577 695.796 l 163.865 696.509 l 131.804 696.509 l h f EMC q 0 18 612 756 re W* n /Artifact <>BDC Q 131.092 684.226 m 164.577 684.226 l 163.865 683.513 l 131.804 683.513 l h f 131.092 684.226 m 131.092 673.226 l 131.804 673.938 l 131.804 683.513 l h f 164.577 684.226 m 164.577 673.226 l 163.865 673.938 l 163.865 683.513 l h f 131.092 673.226 m 164.577 673.226 l 163.865 673.938 l 131.804 673.938 l h f EMC q 0 18 612 756 re W* n /Artifact <>BDC Q 131.092 661.655 m 164.577 661.655 l 163.865 660.943 l 131.804 660.943 l h f 131.092 661.655 m 131.092 650.655 l 131.804 651.367 l 131.804 660.943 l h f 164.577 661.655 m 164.577 650.655 l 163.865 651.367 l 163.865 660.943 l h f 131.092 650.655 m 164.577 650.655 l 163.865 651.367 l 131.804 651.367 l h f EMC q 0 18 612 756 re W* n /Artifact <>BDC Q 131.092 639.085 m 164.577 639.085 l 163.865 638.372 l 131.804 638.372 l h f 131.092 639.085 m 131.092 628.084 l 131.804 628.797 l 131.804 638.372 l h f 164.577 639.085 m 164.577 628.084 l 163.865 628.797 l 163.865 638.372 l h f 131.092 628.084 m 164.577 628.084 l 163.865 628.797 l 131.804 628.797 l h f EMC q 0 18 612 756 re W* n /Artifact <>BDC Q 131.092 616.514 m 164.577 616.514 l 163.865 615.802 l 131.804 615.802 l h f 131.092 616.514 m 131.092 605.514 l 131.804 606.226 l 131.804 615.802 l h f 164.577 616.514 m 164.577 605.514 l 163.865 606.226 l 163.865 615.802 l h f 131.092 605.514 m 164.577 605.514 l 163.865 606.226 l 131.804 606.226 l h f EMC q 0 18 612 756 re W* n /Artifact <>BDC Q 131.092 593.943 m 164.577 593.943 l 163.865 593.231 l 131.804 593.231 l h f 131.092 593.943 m 131.092 582.943 l 131.804 583.656 l 131.804 593.231 l h f 164.577 593.943 m 164.577 582.943 l 163.865 583.656 l 163.865 593.231 l h f 131.092 582.943 m 164.577 582.943 l 163.865 583.656 l 131.804 583.656 l h f EMC q 0 18 612 756 re W* n /Artifact <>BDC Q 131.092 561.797 m 164.577 561.797 l 163.865 561.085 l 131.804 561.085 l h f 131.092 561.797 m 131.092 550.797 l 131.804 551.51 l 131.804 561.085 l h f 164.577 561.797 m 164.577 550.797 l 163.865 551.51 l 163.865 561.085 l h f 131.092 550.797 m 164.577 550.797 l 163.865 551.51 l 131.804 551.51 l h f EMC q 0 18 612 756 re W* n /Artifact <>BDC Q 131.092 539.227 m 164.577 539.227 l 163.865 538.514 l 131.804 538.514 l h f 131.092 539.227 m 131.092 528.226 l 131.804 528.939 l 131.804 538.514 l h f 164.577 539.227 m 164.577 528.226 l 163.865 528.939 l 163.865 538.514 l h f 131.092 528.226 m 164.577 528.226 l 163.865 528.939 l 131.804 528.939 l h f EMC q 0 18 612 756 re W* n /Artifact <>BDC Q 131.092 516.656 m 164.577 516.656 l 163.865 515.944 l 131.804 515.944 l h f 131.092 516.656 m 131.092 505.656 l 131.804 506.368 l 131.804 515.944 l h f 164.577 516.656 m 164.577 505.656 l 163.865 506.368 l 163.865 515.944 l h f 131.092 505.656 m 164.577 505.656 l 163.865 506.368 l 131.804 506.368 l h f EMC q 0 18 612 756 re W* n /Artifact <>BDC Q 131.092 484.51 m 164.577 484.51 l 163.865 483.798 l 131.804 483.798 l h f 131.092 484.51 m 131.092 473.51 l 131.804 474.222 l 131.804 483.798 l h f 164.577 484.51 m 164.577 473.51 l 163.865 474.222 l 163.865 483.798 l h f 131.092 473.51 m 164.577 473.51 l 163.865 474.222 l 131.804 474.222 l h f EMC q 0 18 612 756 re W* n /Artifact <>BDC Q 131.092 461.94 m 164.577 461.94 l 163.865 461.227 l 131.804 461.227 l h f 131.092 461.94 m 131.092 450.939 l 131.804 451.652 l 131.804 461.227 l h f 164.577 461.94 m 164.577 450.939 l 163.865 451.652 l 163.865 461.227 l h f 131.092 450.939 m 164.577 450.939 l 163.865 451.652 l 131.804 451.652 l h f EMC q 0 18 612 756 re W* n /Artifact <>BDC Q 131.092 440.794 m 164.577 440.794 l 163.865 440.081 l 131.804 440.081 l h f 131.092 440.794 m 131.092 429.793 l 131.804 430.506 l 131.804 440.081 l h f 164.577 440.794 m 164.577 429.793 l 163.865 430.506 l 163.865 440.081 l h f 131.092 429.793 m 164.577 429.793 l 163.865 430.506 l 131.804 430.506 l h f EMC q 0 18 612 756 re W* n /Artifact <>BDC Q 131.092 427.799 m 164.577 427.799 l 163.865 427.086 l 131.804 427.086 l h f 131.092 427.799 m 131.092 416.798 l 131.804 417.511 l 131.804 427.086 l h f 164.577 427.799 m 164.577 416.798 l 163.865 417.511 l 163.865 427.086 l h f 131.092 416.798 m 164.577 416.798 l 163.865 417.511 l 131.804 417.511 l h f EMC q 0 18 612 756 re W* n /Artifact <>BDC Q 131.092 405.228 m 164.577 405.228 l 163.865 404.516 l 131.804 404.516 l h f 131.092 405.228 m 131.092 394.228 l 131.804 394.94 l 131.804 404.516 l h f 164.577 405.228 m 164.577 394.228 l 163.865 394.94 l 163.865 404.516 l h f 131.092 394.228 m 164.577 394.228 l 163.865 394.94 l 131.804 394.94 l h f EMC q 0 18 612 756 re W* n /Artifact <>BDC Q 131.092 382.657 m 164.577 382.657 l 163.865 381.945 l 131.804 381.945 l h f 131.092 382.657 m 131.092 371.657 l 131.804 372.37 l 131.804 381.945 l h f 164.577 382.657 m 164.577 371.657 l 163.865 372.37 l 163.865 381.945 l h f 131.092 371.657 m 164.577 371.657 l 163.865 372.37 l 131.804 372.37 l h f EMC q 0 18 612 756 re W* n /Artifact <>BDC Q 131.092 360.087 m 164.577 360.087 l 163.865 359.374 l 131.804 359.374 l h f 131.092 360.087 m 131.092 349.086 l 131.804 349.799 l 131.804 359.374 l h f 164.577 360.087 m 164.577 349.086 l 163.865 349.799 l 163.865 359.374 l h f 131.092 349.086 m 164.577 349.086 l 163.865 349.799 l 131.804 349.799 l h f EMC q 0 18 612 756 re W* n /Artifact <>BDC Q 131.092 337.516 m 164.577 337.516 l 163.865 336.804 l 131.804 336.804 l h f 131.092 337.516 m 131.092 326.516 l 131.804 327.228 l 131.804 336.804 l h f 164.577 337.516 m 164.577 326.516 l 163.865 327.228 l 163.865 336.804 l h f 131.092 326.516 m 164.577 326.516 l 163.865 327.228 l 131.804 327.228 l h f EMC q 0 18 612 756 re W* n /Artifact <>BDC Q 131.092 314.946 m 164.577 314.946 l 163.865 314.233 l 131.804 314.233 l h f 131.092 314.946 m 131.092 303.945 l 131.804 304.658 l 131.804 314.233 l h f 164.577 314.946 m 164.577 303.945 l 163.865 304.658 l 163.865 314.233 l h f 131.092 303.945 m 164.577 303.945 l 163.865 304.658 l 131.804 304.658 l h f EMC q 0 18 612 756 re W* n /Artifact <>BDC Q 131.092 282.799 m 164.577 282.799 l 163.865 282.087 l 131.804 282.087 l h f 131.092 282.799 m 131.092 271.799 l 131.804 272.512 l 131.804 282.087 l h f 164.577 282.799 m 164.577 271.799 l 163.865 272.512 l 163.865 282.087 l h f 131.092 271.799 m 164.577 271.799 l 163.865 272.512 l 131.804 272.512 l h f EMC q 0 18 612 756 re W* n /Artifact <>BDC Q 131.092 260.229 m 164.577 260.229 l 163.865 259.516 l 131.804 259.516 l h f 131.092 260.229 m 131.092 249.229 l 131.804 249.941 l 131.804 259.516 l h f 164.577 260.229 m 164.577 249.229 l 163.865 249.941 l 163.865 259.516 l h f 131.092 249.229 m 164.577 249.229 l 163.865 249.941 l 131.804 249.941 l h f EMC q 0 18 612 756 re W* n /Artifact <>BDC Q 131.092 237.658 m 164.577 237.658 l 163.865 236.946 l 131.804 236.946 l h f 131.092 237.658 m 131.092 226.658 l 131.804 227.37 l 131.804 236.946 l h f 164.577 237.658 m 164.577 226.658 l 163.865 227.37 l 163.865 236.946 l h f 131.092 226.658 m 164.577 226.658 l 163.865 227.37 l 131.804 227.37 l h f EMC q 0 18 612 756 re W* n /Artifact <>BDC Q 131.092 215.088 m 164.577 215.088 l 163.865 214.375 l 131.804 214.375 l h f 131.092 215.088 m 131.092 204.087 l 131.804 204.8 l 131.804 214.375 l h f 164.577 215.088 m 164.577 204.087 l 163.865 204.8 l 163.865 214.375 l h f 131.092 204.087 m 164.577 204.087 l 163.865 204.8 l 131.804 204.8 l h f EMC q 0 18 612 756 re W* n /Artifact <>BDC Q 131.092 192.517 m 164.577 192.517 l 163.865 191.805 l 131.804 191.805 l h f 131.092 192.517 m 131.092 181.517 l 131.804 182.229 l 131.804 191.805 l h f 164.577 192.517 m 164.577 181.517 l 163.865 182.229 l 163.865 191.805 l h f 131.092 181.517 m 164.577 181.517 l 163.865 182.229 l 131.804 182.229 l h f EMC q 0 18 612 756 re W* n /Artifact <>BDC Q /CS0 cs /P0 scn 114.705 30.824 14.249 737.476 re f EMC EMC EMC /Article <>BDC q 0 18 612 756 re W* n 0 0.251 0.502 rg BT /TT0 1 Tf 7.4808 0 0 7.4808 22.0862 757.7553 Tm (Top)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 34.9756 757.7553 Tm ( )Tj /TT0 1 Tf 7.4808 0 0 7.4808 22.0862 744.2187 Tm (Abstract)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 49.5257 744.2187 Tm ( )Tj /TT0 1 Tf 7.4808 0 0 7.4808 22.0862 730.682 Tm (Introduction)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 61.1733 730.682 Tm ( )Tj /TT0 1 Tf 7.4808 0 0 7.4808 22.0862 717.1453 Tm (Methods)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 50.775 717.1453 Tm ( )Tj /TT0 1 Tf 7.4808 0 0 7.4808 22.0862 703.6087 Tm (Results)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 47.0271 703.6087 Tm ( )Tj /TT0 1 Tf 7.4808 0 0 7.4808 22.0862 690.072 Tm (Discussion)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 58.2483 690.072 Tm ( )Tj /TT0 1 Tf 7.4808 0 0 7.4808 22.0862 678.4506 Tm (Commentary: Results may )Tj 0 -1.447 TD (not be widely applicable)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 101.5022 667.6296 Tm ( )Tj /TT0 1 Tf 7.4808 0 0 7.4808 22.0862 654.0929 Tm (Authors' response)Tj /T1_0 1 Tf 9.9744 0 0 9.9744 82.1419 654.0929 Tm ( )Tj ET q 3.5622864 0 0 7.1245575 14.9615784 638.8638 cm /Im0 Do Q 0.502 0.502 0.502 rg BT /TT0 1 Tf 7.4808 0 0 7.4808 18.5239 640.5563 Tm (References)Tj 0 0 1 rg /T1_0 1 Tf 9.9744 0 0 9.9744 56.7731 640.5563 Tm ( )Tj 1 1 1 rg /TT1 1 Tf 10.9718 0 0 10.9718 329.2439 753.7201 Tm (References)Tj 0 0 0 rg /T1_0 1 Tf 7.9795 0 0 7.9795 157.8803 734.7964 Tm (1.)Tj 1.554 0.089 Td (Wald NJ, Kennard A, Hackshaw A, McGuire A. Antenatal screening for Down'\ s syndrome. )Tj /T1_1 1 Tf (J Med Screen. )Tj /T1_0 1 Tf (1997;4:181\226246. )Tj 0 -1.2 TD ([)Tj ET 0 0.314 0.627 RG 0.402 w 10 M 0 j 0 J []0 d 172.934 724.727 m 199.977 724.727 l S 0 0.314 0.627 rg BT /T1_0 1 Tf 7.9795 0 0 7.9795 172.9342 725.9334 Tm (PubMed)Tj 0 0 0 rg (])Tj -1.887 -1.718 Td (2.)Tj 1.554 0.089 Td (Wald NJ, Huttly WJ, Hennessy CF. Down's syndrome screening in the UK in \ 1998. )Tj /T1_1 1 Tf (Lancet. )Tj /T1_0 1 Tf (1999;354:1264. [)Tj ET 520.57 711.732 m 547.612 711.732 l S 0 0.314 0.627 rg BT /T1_0 1 Tf 7.9795 0 0 7.9795 520.5696 712.9382 Tm (PubMed)Tj 0 0 0 rg (])Tj -45.453 -1.718 Td (3.)Tj 1.554 0.089 Td (Wald NJ, Watt HC, Hackshaw AK. Integrated screening for Down's syndrome \ based on tests performed during the first and second )Tj 0 -1.2 TD (trimesters. )Tj /T1_1 1 Tf (N Engl J Med. )Tj /T1_0 1 Tf (1999;341:461\226467. [)Tj ET 320.771 689.161 m 347.813 689.161 l S 0 0.314 0.627 rg BT /T1_0 1 Tf 7.9795 0 0 7.9795 320.7706 690.3676 Tm (PubMed)Tj 0 0 0 rg (])Tj -20.414 -1.718 Td (4.)Tj 1.554 0.089 Td (Nicolaides KH, Snijders RJ, Cuckle HS. Correct estimation of parameters \ for ultrasound nuchal translucency )Tj T* (screening. )Tj /T1_1 1 Tf (Prenat Diagn. )Tj /T1_0 1 Tf (1998;18:519\226523. [)Tj ET 315.448 666.59 m 342.491 666.59 l S 0 0.314 0.627 rg BT /T1_0 1 Tf 7.9795 0 0 7.9795 315.4483 667.797 Tm (PubMed)Tj 0 0 0 rg (])Tj -19.747 -1.718 Td (5.)Tj 1.554 0.089 Td (Wald NJ, Hackshaw AK. Combining ultrasound and biochemistry in first-tri\ mester screening for Down's )Tj T* (syndrome. )Tj /T1_1 1 Tf (Prenat Diagn. )Tj /T1_0 1 Tf (1997;17:821\226829. [)Tj ET 316.342 644.02 m 343.385 644.02 l S 0 0.314 0.627 rg BT /T1_0 1 Tf 7.9795 0 0 7.9795 316.342 645.2263 Tm (PubMed)Tj 0 0 0 rg (])Tj -19.859 -1.718 Td (6.)Tj 1.554 0.089 Td (Hecht CA, Hook EB. The imprecision in rates of Down syndrome by 1-year m\ aternal age intervals: a critical analysis of rates used)Tj ( )Tj T* (in biochemical screening. )Tj /T1_1 1 Tf (Prenat Diagn. )Tj /T1_0 1 Tf (1994;14:729\226738. [)Tj ET 364.65 621.449 m 391.693 621.449 l S 0 0.314 0.627 rg BT /T1_0 1 Tf 7.9795 0 0 7.9795 364.65 622.6557 Tm (PubMed)Tj 0 0 0 rg (])Tj -25.913 -1.718 Td (7.)Tj 1.554 0.089 Td (Wald NJ, Cuckle HS, Densem JW, Nanchahal K, Royston P, Chard T, et al. M\ aternal serum screening for Down's syndrome in )Tj T* (early pregnancy. )Tj /T1_1 1 Tf (BMJ. )Tj /T1_0 1 Tf (1988;297:883\226887. [)Tj ET 311.443 598.879 m 338.485 598.879 l S 0 0.314 0.627 rg BT /T1_0 1 Tf 7.9795 0 0 7.9795 311.4426 600.0851 Tm (PubMed)Tj 0 0 0 rg (])Tj -19.245 -1.718 Td (8.)Tj 1.554 0.089 Td (Wald NJ, Cuckle HS, Densem JW, Kennard A, Smith D. Maternal serum screen\ ing for Down's syndrome: the effect of routine )Tj T* (ultrasound scan determination of gestational age and adjustment for mate\ rnal weight. )Tj /T1_1 1 Tf (Br J Obstet Gynaecol. )Tj /T1_0 1 Tf (1992;99:144\226149. )Tj T* ([)Tj ET 172.934 566.733 m 199.977 566.733 l S 0 0.314 0.627 rg BT /T1_0 1 Tf 7.9795 0 0 7.9795 172.9342 567.9391 Tm (PubMed)Tj 0 0 0 rg (])Tj -1.887 -1.718 Td (9.)Tj 1.554 0.089 Td (Wald NJ, Densem JW, George L, Muttukrishna S, Knight PG. Prenatal screen\ ing for Down's syndrome using inhibin-A as a serum )Tj T* (marker. )Tj /T1_1 1 Tf (Prenat Diagn. )Tj /T1_0 1 Tf (1996;16:143\226153. [)Tj ET 307.469 544.162 m 334.511 544.162 l S 0 0.314 0.627 rg BT /T1_0 1 Tf 7.9795 0 0 7.9795 307.4688 545.3685 Tm (PubMed)Tj 0 0 0 rg (])Tj -19.247 -1.718 Td (10.)Tj 2.054 0.089 Td (Macintosh MC, Wald NJ, Chard T, Hansen J, Mikkelsen M, Therkelsen AJ, et\ al. Selective miscarriage of Down's syndrome )Tj T* (fetuses in women aged 35 years and older. )Tj /T1_1 1 Tf (Br J Obstet Gynaecol. )Tj /T1_0 1 Tf (1995;102:798\226801. [)Tj ET 447.741 521.591 m 474.783 521.591 l S 0 0.314 0.627 rg BT /T1_0 1 Tf 7.9795 0 0 7.9795 447.7406 522.7979 Tm (PubMed)Tj 0 0 0 rg (])Tj -36.826 -1.718 Td (11.)Tj 2.054 0.089 Td (Snijders RJ, Noble P, Sebire N, Souka A, Nicolaides KH. UK multicentre p\ roject on assessment of risk of trisomy 21 by maternal )Tj T* (age and fetal nuchal-translucency thickness at 10-14 weeks of gestation.\ Fetal Medicine Foundation First Trimester Screening )Tj T* (Group. )Tj /T1_1 1 Tf (Lancet. )Tj /T1_0 1 Tf (1998;352:343\226346. [)Tj ET 287.305 489.445 m 314.347 489.445 l S 0 0.314 0.627 rg BT /T1_0 1 Tf 7.9795 0 0 7.9795 287.3046 490.6518 Tm (PubMed)Tj 0 0 0 rg (])Tj -16.72 -1.718 Td (12.)Tj 2.054 0.089 Td (Van der Meulen JHP, Mol BW, Pajkrt E, van Lith JM, Voorn W. Use of the d\ isutility ratio in prenatal screening for Down's )Tj T* (syndrome. )Tj /T1_1 1 Tf (Br J Obstet Gynaecol. )Tj /T1_0 1 Tf (1999;106:108\226115. [)Tj ET 345.587 466.875 m 372.629 466.875 l S 0 0.314 0.627 rg BT /T1_0 1 Tf 7.9795 0 0 7.9795 345.5869 468.0812 Tm (PubMed)Tj 0 0 0 rg (])Tj -24.024 -1.718 Td (13.)Tj 2.054 0.089 Td (Siegel, JE.;Weinstein, MC.; Torrance, GW. Reporting cost-effectiveness s\ tudies and results. In: Gold MR, Siegel JE, Russell LB, )Tj T* (Weinstein MC. , editors. )Tj /T1_1 1 Tf (Cost effectiveness in health and medicine.)Tj /T1_0 1 Tf ( New York: Oxford University Press; 1996. pp. 276\226312.)Tj -2.054 -1.539 Td (14.)Tj 2.054 0.089 Td (Torgerson DJ, Spencer A. Marginal costs and benefits. )Tj /T1_1 1 Tf (BMJ. )Tj /T1_0 1 Tf (1996;312:35\22636. 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[)Tj ET 413.86 387.593 m 440.902 387.593 l S 0 0.314 0.627 rg BT /T1_0 1 Tf 7.9795 0 0 7.9795 413.8596 388.7991 Tm (PubMed)Tj 0 0 0 rg (])Tj -32.58 -1.718 Td (17.)Tj 2.054 0.089 Td (Palomaki GE, Knight GJ, McCarthy JE, Haddow JE, Donhowe JM. TI-Screening\ of maternal serum for fetal Down's syndrome in )Tj T* (the first trimester. )Tj /T1_1 1 Tf (N Engl J Med. )Tj /T1_0 1 Tf (1998;338:955\226961. [)Tj ET 344.262 365.022 m 371.305 365.022 l S 0 0.314 0.627 rg BT /T1_0 1 Tf 7.9795 0 0 7.9795 344.2623 366.2284 Tm (PubMed)Tj 0 0 0 rg (])Tj -23.858 -1.718 Td (18.)Tj 2.054 0.089 Td (Mol BW, Lijmer JG, van der Meulen JHP, Pajkrt E, Bilardo CM, Bossuy PM. \ Effect of study design on the association between )Tj T* (nuchal translucency measurement and Down syndrome. )Tj /T1_1 1 Tf (Obstet Gynecol. )Tj /T1_0 1 Tf (1999;94:864\226869. 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[)Tj ET 320.555 197.452 m 347.598 197.452 l S 0 0.314 0.627 rg BT /T1_0 1 Tf 7.9795 0 0 7.9795 320.5552 198.6587 Tm (PubMed)Tj 0 0 0 rg (])Tj -20.887 -1.718 Td (25.)Tj 2.054 0.089 Td (Gibb DM, MacDonagh SE, Gupta R, Tookey PA, Peckham CS, Ades AE. Factors \ affecting uptake of antenatal HIV testing in )Tj T* (London: results of a multicentre study. )Tj /T1_1 1 Tf (BMJ. )Tj /T1_0 1 Tf (1998;316:259\226261. 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