Screening for fetal Down’s Syndrome – Improving efficacy and efficiency

Review of current service performance Drivers for change Configuration of future service New information and new markers Target performance

Conditions screened for…. Downs Syndrome Neural tube defects Edwards Syndrome

Second trimester performance in South East Scotland 1996 – 2005 Uptake 75% ‘Detection rate’ 66% False positive rate 5.4%

Second trimester performance in South East Scotland 1996 – (34.2%) missed cases 50% of all screened cases with maternal age <35yrs missed 43 amniocentesis performed to diagnose 1 case of Down’s Syndrome

Review of current service performance Drivers for change Configuration of future service New information and new markers Target performance

UK wide…… UK Screening Committee 2001 Numerous publications First and second trimester antenatal screening for Down’s Syndrome: the results of Serum, Urine and Ultrasound Screening Study (SURUSS) 2003 Antenatal Care: routine care for the healthy pregnant woman. NICE 2003 Down’s Serum Screening Quality Assurance Support Service (DQASS) 2004

In Scotland…. CUBS screening for Down’s Syndrome in the 1 st trimester: a Scottish multicentre study. JA Crossley et al 2002 BJOG 109 p 667 Health Technology Assessment Report 5 March 2004 Routine ultrasound scanning before 24 weeks of pregnancy Quality Improvement Scotland Clinical Standards October 2005 Pregnancy and Newborn Screening CEL 31(2008) Changes to Pregnancy and Newborn Screening Programmes

UK Screening Committee bench mark targets….. >75% detection rate for a <3% false positive rate by April 2007 >90% detection rate for a <2% false positive rate by April 2010

Review of current service performance Drivers for change Configuration of future service New information and new markers Target performance

Changes being made to meet new targets and standards Laboratory service on course for central funding from 1/4/10 Laboratory service to be provided from 2 laboratories - Glasgow (Yorkhill) and Edinburgh ( Western General Hospital) First trimester screen for the majority (85%) Enhanced second trimester service (15%) Changing action limit to a higher risk value eg 1:200 or 1:150 Staff training and revision of patient information leaflet

Screening Labs AberdeenGrampian (4.5K)Orkney Shetland Dundee Tayside (2.6K) EdinburghBorders (10K)Fife Lothian GlasgowAyrshire & Arran (20K)Argyll & Clyde Dumfries/Galloway Forth Valley Greater Glasgow Highland Lanarkshire Western Isles

Review of current service performance Drivers for change Configuration of future service New information and new markers Target performance

Screening for Neural Tube Defect using maternal serum AFP Maternal serum AFP measurement will cease to be used to provide the screening service for neural tube defects However There will be an NTD only request form The lab will continue to report AFP MOM and indication of risk with 2 nd trimester results

Markers of fetal Down’s Syndrome Maternal age plus……. First Trimester (11 weeks - 13 weeks and 6 days) Nuchal Translucency (↑) Free beta human chorionic gonadotrophin (↑) Pregnancy-associated plasma protein A (↓) Second Trimester (15 weeks - 20 weeks and 0 days) Intact human chorionic gonadotrophin (↑) Inhibin A (↑) Unconjugated oestriol (↓) Alphafetoprotein (↓)

Request information Demographics Measure of gestation eg CRL/HC and date or EDD Current smoker Ethinic origin Previous affected pregnancy, parenteral history Nuchal translucency and ‘sonographer’ ID Singleton/multiple pregnancy Maternal weight Assisted conception

Marker unaffectedDown’s Syndrome

Marker unaffected Down’s Syndrome 12

Marker unaffected Down’s Syndrome 12

Marker UnaffectedDown’s Syndrome 12

Marker unaffected Down’s Syndrome 12

Importance of accurate dating Dr Trish Chudleigh 2009

CRL conversion 8.052√ (CRL x 1.037) = gestation (days) Robinson HP, Fleming JE,1975 BJOG vol 82; pp

Laboratory standards Daily internal quality control Monthly external quality assessment CPA Accreditation 6 monthly data submission to DQASS Minimum annual work load Licensed risk calculation software Target 3 day turn around time Consultant grade staff heading the service

Nuchal Translucency Measurement performed between 11 weeks 0 days and 13 weeks 6 days Nuchal translucency measured in mm performed routinely on the same day as the blood sample Unique ‘sonographer’ ID number Regular review of operator bias eg DQASS

‘Are you a current smoker’? First trimester effects PAPP-A ↓ 20% Free β hcg → NT → Second trimester effects Total hcg ↓ 18% Inhibin A ↑62% AFP → UE3 →

Demographics

Bar coding the CHI number Bar coded CHI on the request form Label trace software

Sample transport and transit times Postal service/ courier Requirements may differ between 1 st and 2 nd trimester Maximum transit time - 3 days for whole blood Implications for 4 day holidays and samples taken on Thursday Stability of markers in whole blood and serum may be different

Twin Pregnancy NT only - but may change

Review of current service performance Drivers for change Configuration of future service New information and new markers Target performance

Assuming 10,000 screens annually of which 20 are Downs Syndrome pregnancies…… Detection rate False positive rate Amnio or CVS/case detected 13 (66%)539 (5.4%)42/1 15 (75%)299 (3.0%)21/1 18 (90%)200 (2%)12/1

Marker unaffected Down’s Syndrome 12

Team Work Midwives Sonographers Obstetricians Radiologists Radiographers Public Health Consultants Cytogeneticists Clerical staff Biomedical scientists Clinical Scientists IT support Reagent Manufacturers Software Suppliers Engineer support for scanners and analysers etc