Australian and New Zealand Journal of Obstetrics and Gynaecology 2008; 48: 492– 500 DOI: 10.1111/j.1479-828X.2008.00911.x 492 © 2008 The Authors Journal compilation © 2008 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists Blackwell Publishing Asia Original Article Combining first and second trimester markers for Down syndrome screening: Think twice Robert COCCIOLONE, 1 Kate BRAMELD, 4,5 Peter O’LEARY, 4,6,7 Eric HAAN, 1 Peter MULLER 2 and Karen SHAND 3 1 Department of Genetic Medicine and Department of Paediatrics, University of Adelaide, Adelaide, South Australia, 2 Perinatal Medicine, Women’s and Children’s Hospital, North Adelaide, South Australia, 3 Ultrasound Specialists for Women, Ashford Specialist Centre, Ashford, South Australia, 4 Office of Population Health Genomics, Department of Health (WA), Perth, Western Australia, 5 Schools of Population Health and 6 Women’s and Infants’ Health, University of Western Australia, Crawley, Western Australia, and 7 School of Public Health, Division of Health Sciences, Curtin University of Technology, Perth, Western Australia, Australia Aims: This study compares different screening strategies for the detection of Down syndrome and considers practical implications of using multiple screening protocols. Methods: The performance characteristics of each screening strategy were assessed based on datasets of Down syndrome (n = 11) and unaffected pregnancies (n = 1006) tested in both first and second trimester, as well as data from first trimester (n = 18 901) and second trimester (n = 40 748) pregnancies. Results: For a detection rate of 91%, the false positive rates for integrated and serum integrated screening were 2.5% and 6.3%, respectively, compared with combined first trimester (4.6%) and second trimester (12.6%) screening. Contingent and sequential screening protocols achieved detection rates of 82 to 91% with false positive rates between 2.6 and 2.9%. Contingent protocols require retesting of 15 to 20% of cases in the second trimester. Sequential and integrated protocols require retesting of 98 to 100% of cases in the second trimester. The various screening strategies did not always detect the same Down syndrome pregnancies. Conclusions: Combining first and second trimester markers for Down syndrome screening better defines the at-risk population. However, integrated protocols complicate management of screening programs and may not be suitable as primary screening strategies. It may be a better use of resources to refine current first and second trimester programs through improved access and new markers. We therefore suggest thinking twice before embracing integrated population screening programs. Key words: Down syndrome, integrated contingent, first trimester screening. Introduction There have been population-based second trimester antenatal screening programs for Down syndrome and other fetal anomalies in Australia since 1991. 1 First trimester combined screening was introduced in 2000 in Australian and several studies 2–5 have demonstrated first trimester program performances (detection rate (DR) 83–87% for a 5% false positive rate (FPR)) comparable with international groups. 6–8 The majority (78%) of women who undertook screening tests in Australia in 2004 opted for first trimester screening. 9 Multiple factors determine which programs women access. Availability of appropriate ultrasound facilities, gestational age at presentation, awareness that there is a choice of screening tests, doctor preference and hospital guidelines all play a part. Currently Australian policy guidelines recommend that women should be made aware of the availability of first and second trimester screening tests for Down syndrome and other chromosomal abnormalities. 10 However, professional organisations in Canada, 11 the USA 12 and the UK 13 have proposed that women be given a choice of alternative strategies that include integrated, 14 contingent 15,16 or sequential 17 screening. The Down syndrome screening protocols reviewed are outlined in Table 1. Integrated, contingent and sequential protocols are based on fetal nuchal translucency (NT) thickness and maternal serum pregnancy-association plasma protein-A (PAPP-A) measurements in first trimester and either triple or quadruple maternal serum markers in the second trimester. Integrated screening involves withholding risk odds until second trimester testing is complete. 7 This approach is controversial as women do not have the option of early Correspondence: Mr Robert Cocciolone, Antenatal Screening (SAMSAS) Program, Genetic Medicine, 72 King William Road, North Adelaide, SA 5006, Australia. Email: robert.cocciolone@cywhs.sa.gov.au Received 14 February 2008; accepted 13 April 2008.