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In order to explore the impact of potential new technologies in the area of prenatal screening, we conducted a baseline study using qualitative interviews to explore women's attitudes and knowledge regarding current and future prenatal screening technology and methods. Three cohorts were interviewed, including healthy women without children, healthy women with healthy children, and healthy women with children who have de novo genetic disorders. This study aimed to assess the baseline understanding and attitudes of women in Western Australia. Women from each cohort demonstrated adequate knowledge of the differences between screening and diagnostic tests, but were mostly unaware of the conditions for which screening is currently available except Down syndrome. Women who had children with de novo genetic conditions were generally aware of more genetic conditions than women with or without healthy children. Most women recognised the genetic basis for the conditions mentioned. Two thirds of women understood that Down syndrome is a chromosomal condition; just one third recognised that the phenotype is variable. Most women expressed a positive attitude towards Down syndrome. Social acceptance of children with Down syndrome was commonly mentioned as a concern. While the majority of women with children supported screening for Down syndrome, they emphasised that it must be an autonomous choice. General knowledge of genetic conditions illustrated that women are exposed to diverse conditions from lived experience as well as the media.

Background: Contingent screening for trisomy 21 using non-invasive prenatal testing has the potential to reduce invasive diagnostic testing and increase the detection of trisomy 21., Aim: To describe the diagnostic and economic performance of prenatal screening models for trisomy 21 that use non-invasive prenatal testing as a contingent screen across a range of combined first trimester screening risk cut-offs from a public health system perspective., Methods: Using a hypothetical cohort of 300 000 pregnancies, we modelled the outcomes of 25 contingent non-invasive prenatal testing screening models and compared these to conventional screening, offering women with a high-risk (1 > 300) combined first trimester screening result an invasive test. The 25 models used a range of risk cut-offs. High-risk women were offered invasive testing. Intermediate-risk women were offered non-invasive prenatal testing. We report the cost of each model, detection rate, costs per diagnosis, invasive tests per diagnosis and the number of fetal losses per diagnosis., Results: The cost per prenatal diagnosis of trisomy 21 using the conventional model was $51 876 compared to the contingent models which varied from $49 309-66 686. The number of diagnoses and cost per diagnosis increased as the intermediate-risk threshold was lowered. Results were sensitive to trisomy 21 incidence, uptake of testing and cost of non-invasive prenatal testing., Conclusion: Contingent non-invasive prenatal testing models using more sensitive combined first trimester screening risk cut-offs than conventional screening improved the detection rate of trisomy 21, reduced procedure-related fetal loss and could potentially be provided at a lower cost per diagnosis than conventional screening., (© 2017 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Antenatal screening for fetal anomalies has provided women and their partners with information to make reproductive choices based on the risk of serious chromosomal or structural defects since the 1990s. Alternative tests include first-trimester screening (combined ultrasound and maternal serum markers), second-trimester maternal serum markers and noninvasive cell-free DNA testing. The recent recommendations by the Royal Australian and New Zealand College of Obstetrics and Gynaecology and the Human Genetics Society of Australasia against second-trimester triple testing are based on unsound performance criteria, raise several contestable issues around access and equity and challenge the principles of governments providing affordable options., (© 2015 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Objective: To provide data on how screen-positive and detection rates of first trimester prenatal screening for fetal Down syndrome vary with changes in the risk cut-off and maternal age to inform contingency criteria for publicly funded noninvasive prenatal testing., Materials and Methods: First trimester screening and diagnostic data were collected for all women attending for first trimester fetal aneuploidy screening in Western Australia between 2005 and 2009. Prenatal screening and diagnostic data were linked to pregnancy outcomes, including data from the Midwives' Notification System and the Western Australian Registry of Developmental Anomalies. The prevalence of Down syndrome and performance of screening by risk cut-off and/or for women >35 years were analysed., Results: The current screening risk cut-off of 1:300 has screen-positive and detection rates of 3.5% and 82%. The screen-positive rate increases by 0.7-0.8% for each 100 point change in risk, up to 19.2% at 1:2500 (96% detection rate). Including all women >35 years as screen positive would increase the screen-positive rate and detection rates to 30.2% and 97.2%., Conclusion: Variation in screening risk cut-off and the use of maternal age to assess eligibility for noninvasive testing could significantly impact the demand for, and cost of, the test. A contingent first trimester screening approach for risk assessment is superior to the use of a combination of screening and maternal age alone. These data will inform decisions regarding the criteria used to determine eligibility for publicly funded noninvasive prenatal testing., (© 2016 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Objective: To assess how prenatal screening and diagnostic testing have impacted the diagnosis, termination and birth prevalence of Down syndrome in Western Australia (1980-2013)., Method: We analysed trends in termination rates and birth prevalence of Down syndrome using aggregated data (1980-2013). We modelled the expected live-birth rate and prevalence of Down syndrome and compared different eras of screening and diagnosis with respect to the impact on live-birth rate and prevalence of Down syndrome., Results: Between 1980 and 2013, the rate of Down syndrome pregnancies increased, corresponding to a greater proportion of babies born to older women. Following the introduction of screening in 1994, the rate of live-born infants with Down syndrome reduced significantly (p = 0.001). The rate of terminations of pregnancy for Down syndrome remained stable over this period. In the absence of termination, the Down syndrome live-birth rate would have risen from 1.1 per 1000 to 2.17 per 1000 between 1980 and 2013., Conclusion: Prenatal testing in Western Australia has reduced the birth prevalence of Down syndrome despite an increased rate of Down syndrome pregnancies. Most women for whom a prenatal diagnosis of fetal Down syndrome is made, chose to terminate the pregnancy (93%), and this proportion has not changed over the study period., (© 2015 John Wiley & Sons, Ltd.)

Objective: To analyse the cost-effectiveness and performance of noninvasive prenatal testing (NIPT) for high-risk pregnancies following first-trimester screening compared with current practice., Methods: A decision tree analysis was used to compare the costs and benefits of current practice of first-trimester screening with a testing pathway incorporating NIPT. We applied the model to 32 478 singleton pregnancies screened between January 2005 and December 2006, adding Medicare rebate data as a measure of public health system costs. The analyses reflect the actual uptake of screening and diagnostic testing and pregnancy outcomes in this cohort., Results: The introduction of NIPT would reduce the number of invasive diagnostic procedures and procedure-related fetal losses in high-risk women by 88%. If NIPT was adopted by all women identified as high risk by first-trimester combined screening, up to 7 additional Down syndrome fetuses could be confirmed. The cost per trisomy 21 case confirmed, including NIPT was 9.7% higher ($56,360) than the current prenatal testing strategy ($51,372) at a total cost of $3.91 million compared with $3.57 million over 2 years., Conclusion: Based on the uptake of screening and diagnostic testing in a retrospective cohort of first-trimester screening in Western Australia, the implementation of NIPT would reduce the number of invasive diagnostic tests and the number of procedure-related fetal losses and increase the cost by 9.7% over two years. Policy planning and guidelines are urgently required to manage the funding and demand for NIPT services in Australia., (© 2013 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Aim: To identify first trimester indicators of adverse pregnancy outcomes., Method: Data were obtained from the statewide evaluation of first trimester screening for Down syndrome in Western Australia which included 22,695 pregnancies screened between August 2001 and October 2003. Screening data were linked with pregnancy outcome information from the Hospital Morbidity Database and the Birth Defects Registry. The odds ratios (OR) of adverse outcomes were analysed for combined risk incorporating maternal age, nuchal translucency (NT) and biochemical parameters and then separately for each parameter (pregnancy-associated plasma protein-A (PAPP-A), free beta human chorionic gonadotropin (beta-hCG) and NT)., Results: Risk assessments for first trimester combined screening are derived from maternal age, ultrasound measurement of fetal NT, maternal serum free beta-hCG and PAPP-A. Increased combined risk for Down syndrome was significantly (P < 0.01) associated with spontaneous loss at or before 24 weeks gestation (OR 13.51), birth defects (OR 6.58) and preterm birth at or before 32 weeks gestation (OR 3.2). Maternal serum PAPP-A below the 5th centile was associated with Down syndrome (OR 8.43), spontaneous loss before 24 weeks (OR 5.04) and later than 24 weeks (OR 4.50), preterm delivery before 32 weeks (OR 3.11) and before 37 weeks (OR 2.24). NT above the 95th centile was associated with Down syndrome (OR 43.91), birth defects (OR 4.02) and spontaneous loss before 24 weeks (OR 6.24). Low levels of free beta-hCG and increased NT were less consistently associated with adverse outcomes and high levels of free beta-hCG showed limited use as an indicator. The detection rates for all outcomes other than Down syndrome were less than 40%., Conclusion: Biochemical indicators and NT that are measured during first trimester screening for Down syndrome show a number of associations with adverse outcomes, but do not show appropriate performance characteristics for screening tests. These data are consistent with the view that the individual components, specifically low PAPP-A levels alone, do not provide an effective screening tool for adverse pregnancy outcomes.

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.

Background: A relatively few centres across Australia provide screening tests for maternal serum markers or ultrasound measurement of fetal nuchal translucency to assess risk of fetal anomalies such as Down syndrome. While providers engage in external accreditation and quality assurance programs, state and federal governments have been slow to formulate relevant policies and standards., Aim: In this paper we review the current practices across Australian states and territories and propose recommendations for developing a national policy framework., Methods: Data on the number and types of screening tests provided as well as state policies, where they are available, were obtained from government reports and supplemented by a mail survey to selected stakeholders in each state or territory., Results: At a jurisdictional level, our results highlight the need to integrate the collection and monitoring of antenatal population-screening programs to assess clinical effectiveness and program performance (detection and screen-positive rates, uptake of diagnostic tests as a result of screening). Women's expectations and satisfaction with the information they are provided should be evaluated and used to adjust education resources. At a local level, collaboration between providers of the separate tests, both public and private, would enable the ascertainment of outcomes of integrated screening programs. To complete the cycle, these data should inform decisions to improve antenatal screening programs at a national level., Conclusions: A primary goal at a national level would be to develop a consensus on key performance indicators for programs that clarify best practice guidelines and establish optimal performance and accreditation standards.

Objective: This study assessed fetal outcomes for pregnancies identified at increased risk for Down syndrome by first-trimester combined ultrasound examination and maternal serum biochemistry screening., Methods: First-trimester combined screening data were obtained from ultrasound clinics across Western Australia between August 2001 and October 2003. Prenatal screening data were linked with pregnancy outcome information held in state health database registers using probabilistic record-linkage techniques., Results: In 50 of the 60 pregnancies affected by Down syndrome, the adjusted risk was greater than 1 in 300, providing a detection rate of 83% (95% confidence interval [CI] 74-93%). Among all women screened (n = 22,280), 827 had increased risk results but did not have a Down syndrome pregnancy, representing a false-positive rate of 3.7% (95% CI 3.5-3.9%). Ten cases of Down syndrome were detected among women considered not at increased risk, consistent with a false-negative rate of 1 in 2,227. First-trimester combined screening reduced the number of Down syndrome births by 50 in 22,280 (2.24 cases per 1,000 births), which represents the detection of one case of fetal Down syndrome for every 446 women screened. Furthermore, 25% of pregnancies with other birth defects occurred among those identified at increased risk of Down syndrome, and 1 in 8 pregnancies at increased risk were found to have a significant chromosomal or structural defect., Conclusion: First-trimester combined screening in Western Australia detected 83% (95% CI 74-93%) of Down syndrome pregnancies at a 3.7% (95% CI 3.5-3.9%) false-positive rate., Level of Evidence: II-2.