1. Expanded newborn screening update Prof Jim Bonham Clinical Director Sheffield Children’s NHS FT

2. Screening Results 1 st & 2 nd Quarter Number of expanded screening declines across the six sites: 193 (0.06%) Number of Expanded Screening Declines Number of Births Site1st Quarter Births2nd Quarter BirthsTotal Births Birmingham19,48518,48437,969 Great Ormond Street33,97032,06166,031 Guy's & St Thomas'16,59914,61731,216 Leeds12,07512,50524,580 Manchester15,54014,14129,681 Sheffield19,17819,44638,624 Total Births116,847111,254228,101 Estimated Births for 8 months = 304,134 Site 16/07 17/08 18/08 17/09 18/09 17/10 18/10 17/11 18/11 17/12 18/12 17/01 18/01 17/02 18/02 17/03 Site Totals Birmingham121012340133 Great Ormond Street141394625154 Guy's & St Thomas'3012010 1 8 Leeds111200005 Manchester12154543236 Sheffield22795434357 Total Declines643226191814128193

3. What were our expectations? ConditionPrevalence Screen positives True positives False positivesPPV% MSUD 1:116,00084450 HCys 1:144,00083538 GA1 1:109,191104640 IVA 1:155,396103730 LCHAD 1:218,56452340 TOTAL 1:28,00041162539

4. BirminghamMSUDHycsIVAGA1LCHADD TOTAL Expected by this time False positives102003 True positives101002 Sibling identified case001001 GOSH False positives001001 True positives000202 Sibling identified case000000 Guy ’ s & St Thomas ’ False positives002002 True positives000101 Sibling identified case000000 Leeds False positives001001 True positives010001 Sibling identified case000000 Manchester False positives000000 True positives000000 Sibling identified case001001 Sheffield False positives002002 True positives002002 Sibling Identified case000011 TotalMSUDHycsIVAGA1LCHADDTotal Expected False positives108009 17.7 True positives113308 11.3 PPV%4739 What have we found so far? (Jason Sowter)

5. Website Usage (Clare Gibson) The number of unique visitors per month has remained steady for the five months a rise was seen in February. There is a little fluctuation on the number of true visitors (defined as remaining at the website for more than 30 seconds) The majority of visitors spend less than 30 seconds at the site

6. Website Usage – Accessing translations Translated versions of the Parent & Health Professional leaflet have been accessed a total of 166 times in 8 different languages. Polish is the most commonly downloaded translation, followed by Turkish. Urdu is the only audio translation to be accessed (a total of 9 times)

7. Website Updates – The revised website

8. Website Updates The new website includes: Simplified information about each of the 5 conditions Access of all information for all (i.e. removal of the password restricted area) A suite of short films (produced in partnership with Optical Jukebox) describing the role of newborn screening and each of the five conditions Simplified access to important information – such as leaflet ordering and leaflet translations Front page links to other key websites (BIMDG and NSPC) An improved navigation structure including a search facility and bread crumbs The new website and the films were released at the Rare Diseases Day Parliamentary Reception at Houses of Parliament on 27th February 2013.

9. Website Usage - Queries 26 queries from NHS staff, 7 from members of public. Initial response times within 3 day time bracket. Most common query – ordering leaflets Midwives, health visitors & screening co-ordinators most common profession.

10. Issues to explore? Improving the assays Mild disease, particularly the IVA’s Evaluating the impact of false positive results Bridging work

11. Improving the assays EQA, Final Mackenzie Population data, Rodney Pollitt and Rachel Carling Circulation of samples with Int Std kit to identify analyser related variables, Rachel Carling

12. Mild disease, particularly the IVA’s  The issue  Two mild IVA’s in the first month  One of these includes the mild mutation  The other the child is well, consanguineous kindred, C5 at screening was 1.11 µmol/L (cut-off 1.00 µmol/L)  Urinary IVG modest  54.6 µmol/mmol cr  Infant control range : 0.06 – 1.20 (n=12)  Mild mutation : 23 – 79 (n=2)  Symptomatic patients : 685 - 4,541 (n=9)  Treated conservatively on emergency regimen, older siblings being tested Further study  Do we need to look carefully at “mild case/ mutation experience” in similar populations eg UK/Netherlands/Germany and determine if we can stratify risk on a biochemical basis – metabolite or enzyme assay?

13. Evaluating the impact of false positives The problems  Parents tell us that false positives are not a huge problem in theory - Dixon S JIMD 2012  In practice the evidence is somewhat contradictory  Tu WJ PLoS One 2012 39% of mothers with a false +ve result describe concerns about child’s future development vs 10% in the normal screened group  Waisbren SE et al JAMA 2003 Children with FP result twice as likely to experience hospitalisation 21% vs 10% and mothers report increased PSI score p<0.001 Vs  Lipstein EA Genet Med 2009 200 children with FP and 137 normal showed no difference in healthcare utilisation  Prosser LA Arch Pediatr Adol Med 2008 91 parents with FP result vs 50 with a normal. Demonstrated a high tolerance in a WTP study  Why is this and what do the parents want?  Many studies tell us that better communication reduces stress  Generally studies do not compare how the family was given the news or supported in the time to confirmation

14. Evaluating the impact of false positives A planned study, Dr Louise Moody  A detailed literature search  Identification of key issues that may confound studies  Determine the views of parents who have received a false positive screening result  Determine the views of parents who have received a true positive screening result  Determine the views of metabolic physicians, metabolic nurses and dietitians have delivered a result  Make reccomendations for best practice To begin in July 2013, complete in 2014

15. Bridging work Resources for patients  Videos  Podcast use  Written material  Website  Help line Resources for professionals  The diagnostic process and organisation of testing  Telemedicine support  Case definitions  Treatment protocols for a spectrum of disease

16. For the future Continuing the study after July 2013 Completing the CRF data collection and health economic evaluation (Prof Jim Chilcott, ScHARR) Presentation to the UKNSC Considering further conditions to be included and creating a northern European consensus – Literature search and meeting Continuing to develop the website - CLAHRC2 CAH – RFPB application