1. What CARs can tell us about screening programmes & their population effects: a model for trisomy 21 Ann M Tonks (WMCAR PHE), Adam S Gornall (The Shrewsbury & Telford Hospital NHS Trust)

2. Background Congenital anomaly surveillance & screening are both population-based public health activities CARs collect affected cases from the total/target population; including the screened and unscreened cohorts Screening detection rates (DTRs) are needed to provide women with information to make informed choices monitor performance Modelled DTRs for T21 screening tests are available from DQASS for service-based (laboratory) cohorts only There is a paucity of data on the total population effects and performance of screening programmes 2WMCAR T21 BINOCAR 2014

3. Methods - CARs T21 cases were identified from a regional BINOCAR register (WMCAR) Population-based data using multiple sources and active case-finding Systems that do not actively collect all postnatally identified cases (unscreened and screen –ve cases) will: UNDER-estimate prevalence OVER-estimate detection rates Reliable methodology, generates good quality data and ensures highest possible ascertainment † † Savva G M, Morris J K. Ascertainment and accuracy of Down syndrome cases reported in congenital anomaly registers in England and Wales. Arch Dis Child Fetal Neonatal Ed 2009; 94: F23–F27. 3WMCAR T21 BINOCAR 2014

4. Methods – T21 WMCAR Setting West Midlands: annual birth population of ≈ 73,500, 15 Acute Trusts T21 screening – combined or quad screening (Jan 2011+) Case definition All cytogenetically confirmed T21 cases: screened (NHS & private) & unscreened Selected by EDD (Jul 2011-Jun 2013) & postcode at delivery All outcomes miscarriages, TOPs (all gestations), & registerable births Affected population, excludes screen +ve cases where karyotyping normal/declined 4WMCAR T21 BINOCAR 2014

5. Methods – T21 data collection/validation Prospective reporting of cases by Trusts (via Local LCO) or other sources Diagnoses/ascertainment validated with cytogenetics labs (regional & private), NDSCR annual, surrounding CARs Retrospective validation of cases by Trusts (LCOs): a) correctly allocated to Trust at booking b) details of the screening offer/results collected Screened:screening data are confirmed with biochemistry labs Unscreened: choices confirmed in maternal notes or dating USS confirm eligibility – late bookers or IUD at dating Provisional Trust lists of T21 cases are sent to LCOs for cleaning 5WMCAR T21 BINOCAR 2014

6. Results - CARs 397 cases of T21 (2 years) Total prevalence 25.9 / 10,000 births (95%CI 24.2-29.5) Median mat age at EDD (36, IQR 31-40); background (all births) 28 years Live births, n=202 (50.9%) Live birth prevalence 13.1 / 10,000 live births (95%CI 11.3-14.9) Mortality: stillbirths and infant deaths, n= 28 6WMCAR T21 BINOCAR 2014

7. 7 Combined (81.5%) DTR72.4% (65.9-78.9) MOBP90%/2% Quad DTR63.4% (48.7-78.2) MOBP75%/3% NHS SCREENED n=222 screen-ve n=65 Screen DTR 70.7% (64.7-76.7) 75.1% DIAGNOSES NHS screening n=118 screen+ve n=157 PND56.3% (49.8-62.8)

8. Results: combined screening DTR 8WMCAR T21 BINOCAR 2014

9. Results: maternal ethnic group 9WMCAR T21 BINOCAR 2014 White BritishOther Total affected T21292105 Median mat age EDD (IQR) yrs 37 (31-40) 36 (31-39) Screening uptake in eligible, p<0.01 63.0% (57.3-68.6) 46.9% (36.9-56.9) NHS screen DTR, p=0.05 74.0% (67.6-80.5) 57.8% (43.3-72.2) Uptake PND in screen +ve77.9%61.5% Population PND rate, p<0.01 54.8% (49.1-60.5) 28.6% (19.9-37.2) Uptake TOP following PND 85.0% (79.5-90.5) 90.0% (79.3-100)

10. Results: CAR outcomes (total) 10WMCAR T21 BINOCAR 2014 Prevalence: total & live birth, long term trends Pregnancy outcomes, mortality rates, long term survival Link to exposures (fluoridation) Population PND rates timing of prenatal diagnosis methods of invasive testing Workload/work force planning

11. Results: screening tests & programme 11WMCAR T21 BINOCAR 2014 Population-based (e.g. Area Team) or service-based (e.g. booked at Trust) Screened cohort: Which type of test? %combined v %quad Test performance (DTR) – observed not modelled Pathway activity – uptake of PND, uptake of TOP Screening Programme: Eligible population size Offer coverage/screening uptake (affected group only) Missed screen (eligible cases screening not offered/completed)

12. Results: stakeholders 12WMCAR T21 BINOCAR 2014 Trusts: Case list for Annual Antenatal & Newborn Screening Audit Submission Missed screen SSS screen –ve (combined) image review Summary report for Trust Screening Board Area Team: Screening outcomes Screening lab: Own DTR Audit and review of screen –ve cases

13. Conclusions CARs provide a picture of screening performance and its population effects in affected cases Quantify the benefits of screening, but not the risks. CARs can generate reliable service and population-based screening outcomes for an entire programme or a specific test within it. There is an opportunity to use routinely-collected CAR data to inform other antenatal screening programmes. West Midlands Combined screening DTR did not achieve the NSC MOBP. Population prenatal diagnosis rates varied by maternal ethnic group. 13WMCAR T21 BINOCAR 2014

14. Acknowledgements All clinical, laboratory, and administrative staff who notify WMCAR, especially Local Screening Co-ordinators WMCAR staff for processing, coding, completing notifications 14WMCAR T21 BINOCAR 2014

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16. Trisomy 21 prenatal diagnosis (karyotype) 16Presentation title - edit in Header and Footer

17. 17WMCAR & T21 CKO visit

18. T21 prenatal diagnosis timing

19. Invasive procedure activity

20. Headings are set in 40 pt Arial Large body copy should be set in 18pt Roman Large subheadings set in 18pt Arial Text 20Presentation title - edit in Header and Footer

23. SURUSS & Private vs NHS