Expanded newborn screening update

Prof Jim Bonham Clinical Director

Sheffield Children’s NHS FT

Screening Results 1st & 2nd Quarter

Number of expanded screening declines across the six sites: 193 (0.06%)

Number of Expanded Screening Declines

Number of Births

Site 1st Quarter Births 2nd Quarter Births Total Births

Birmingham 19,485 18,484 37,969

Great Ormond Street 33,970 32,061 66,031

Guy's & St Thomas' 16,599 14,617 31,216

Leeds 12,075 12,505 24,580

Manchester 15,540 14,141 29,681

Sheffield 19,178 19,446 38,624

Total Births 116,847 111,254 228,101 Estimated Births for 8 months = 304,134

Site16/0717/08

18/08 17/09

18/0917/10

18/10 17/11

18/1117/12

18/1217/01

18/01 17/02

18/02 17/03

Site Totals

Birmingham 12 10 1 2 3 4 0 1 33

Great Ormond Street 14 13 9 4 6 2 5 1 54

Guy's & St Thomas' 3 0 1 2 0 1 0 1 8

Leeds 1 1 1 2 0 0 0 0 5

Manchester 12 1 5 4 5 4 3 2 36

Sheffield 22 7 9 5 4 3 4 3 57

Total Declines 64 32 26 19 18 14 12 8 193

What were our expectations?

Condition PrevalenceScreen

positivesTrue

positivesFalse

positives PPV%

MSUD 1:116,000 8 4 4 50

HCys 1:144,000 8 3 5 38

GA1 1:109,191 10 4 6 40

IVA 1:155,396 10 3 7 30

LCHAD 1:218,564 5 2 3 40

TOTAL 1:28,000 41 16 25 39

Birmingham MSUD Hycs IVA GA1 LCHADD TOTALExpected by

this time

False positives 1 0 2 0 0 3

True positives 1 0 1 0 0 2

Sibling identified case 0 0 1 0 0 1

GOSH            

False positives 0 0 1 0 0 1

True positives 0 0 0 2 0 2

Sibling identified case 0 0 0 0 0 0

Guy’s & St Thomas’            

False positives 0 0 2 0 0 2

True positives 0 0 0 1 0 1

Sibling identified case 0 0 0 0 0 0

Leeds            

False positives 0 0 1 0 0 1

True positives 0 1 0 0 0 1

Sibling identified case 0 0 0 0 0 0

Manchester            

False positives 0 0 0 0 0 0

True positives 0 0 0 0 0 0

Sibling identified case 0 0 1 0 0 1

Sheffield            

False positives 0 0 2 0 0 2

True positives 0 0 2 0 0 2

Sibling Identified case 0 0 0 0 1 1

Total MSUD Hycs IVA GA1 LCHADD Total Expected

False positives 1 0 8 0 0 9 17.7

True positives 1 1 3 3 0 8 11.3

PPV% 47 39

What have we found so far? (Jason Sowter)

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

Graph depicting number of visitors to expandedscreening.org

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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)

Website Updates – The revised website

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.

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.

Number of Days taken to Respond to Website Query (May 2012 - March 2013)

0

5

10

15

20

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0 Days 1 Day 2 Days 3 Days

Query Type

31%

18%

9%

9%

3%

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12%

3%3%

3%3% 3% Leaflets

Access to restricted areas

Translations

Website error

General information

CHRD

Study areas

Diagnostic pathway

Junk mail

Blood spot response time

How to participate

CF screening

Issues to explore?

Improving the assays

Mild disease, particularly the IVA’s 

Evaluating the impact of false positive results

Bridging work

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

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?

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

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

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

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