1. Newborn screening Dr Jim Bonham Clinical Director
Sheffield Children’s NHS FT 1

2. Outline What is screening and why is it different?
The organisation of screening
MCAD deficiency
Expanded newborn screening
Outcome data
Who chooses and why?
What are the tasks ahead?
What about other disorders and what about the future?
What is the role of CLIMB?
The IMD App 2

3. Why is it different?
The patients/families believe themselves to be well and this gives us a particular burden of responsibility
The initial test does not in itself give a definitive answer. It simply separates those who are more likely to have the condition (and require follow-up) from those who are less likely to have it
“All screening programmes do harm; some do good as well, and, of these, some do more good than harm….” Gray, BMJ (2008) 336:480 3

4. How do we organise screening in the UK?
It is organised and supported as part of the NHS
There are 16 screening labs testing 30,000 – 130,000 babies per year
Samples are collected at home by midwives on day 5-8
They are transported by mail to the laboratory
Analysed on the following day
Reported by post to Child Health Record departments
Patient referrals made by the Lab to relevant physicians for treatment
The process is governed by agreed national targets

5. The History of Newborn Screening in the UK
PKU began in 1969, around 60 babies detected each year, would otherwise be severely mentally disabled, can develop normally on a low phenylalanine diet.
A total of approximately 2300 detected so far.
Annual cost of residential care would be £ 60m pa
Annual cost of treatment + screening program = £8m
Typically 60 cases per year detected in 750k annual births

6. So what about the other disorders?
MCAD deficiency introduced in 2004
MCAD deficiency
A life threatening condition
Difficult to detect clinically
Good screening test C8
Reliable confirmation in most cases
Safe effective and simple treatment
Approx 70 cases pa

7. What about other IMD’s ?
A growing clinical recognition that early detection improves outcome in IMD’s
The widespread international adoption of expanded newborn screening, with ten countries in Europe screening for ten or more disorders
Concern to identify potential dysbenefits of screening for IMDs
Funding from CLAHRC in 2008 for five years to implement research findings into widespread practice
Selection of a limited number (five disorders) of conditions that appeared on most lists and gained a consensus within the UK: GA1, MSUD, IVA, Hcys, LCHADD 7

8. The consultation and the decision
The responses
Organisations
Number
Trusts 10
Professional groups 6
Parent groups 2
Overseas
Individuals 1
Other - PHG, CRG
All except one suggested all five should be included
and the start date was 5th January 2015

9. 2014-2016 data – 1.235m births Prevalence True positives
Condition
Prevalence
True positives
False positives
PPV%
Expected at outset
Actual data
Expected
MSUD
1:140k
1:176k 9 7 4 50 64
HCU
1:204k
1:308k 6 5 38 44
GA1
1:96k
1:309k 13 40
IVA
1:123k
1:137k 10
3+6 20 30 60
Total
1:27k
1:51k 24 39 21 53

10. 2012-2016 data – Sensitivity - provisional
Disorder
Screen detected
Prospective testing
Clinically detected
Sensitivity
(%)
MSUD 14 6 70
HCU 9 1
100
GA1 15 3 83
IVA 13 4

11. Who chooses and why? It varies in different countries
In the USA it is the ACMG
In many countries in Europe it is government working with health insurers and health professionals
In the UK, the National Screening Committee advises ministers, there is a strong representation from Public Health
Standards are set and monitored by Public Health England and the services are commissioned by NHS England
So - how do they choose?
the condition screened for should be an important one
there should be an acceptable treatment for patients with the disease
the facilities for diagnosis and treatment should be available
there should be a recognised latent or early symptomatic stage
there should be a suitable test or examination which has few false positives – specificity
and few false negatives – sensitivity
the test or examination should be acceptable to the population
the cost, including diagnosis and subsequent treatment, should be economically balanced in relation to expenditure on medical care as a whole 11

12. The tasks ahead Gathering longer term data on progress
Identifying the cases
UKNSPC data collection
MetBioNet data collection on clinically identified cases
Involving the clinicians to make an assessment
Reducing the side effects
Preparing materials to support families with screen positive cases, the App that Oliver will talk about
Getting communication and consent right before screening, recent HTA study, Fiona Ulph
Organising referral in the best possible way, current HS&DR study, Jane Chudleigh
Using IT to speed up the system
The e-red book project 12

13. What about other disorders and the future ?
Other disorders under consideration
Severe Combined Immune Deficiency
X-linked adrenoleukodystrophy
Tyrosinaemia type 1
mucopolysacchariodoses
Different approaches
Using genetic techniques
In addition to the current screening
As an alternative
Health Innovation Challenge Fund

14. Health Innovation Challenge Fund
The role of CLIMB
Helping to think about and design research questions
Helping to design the research study
Taking part in the research
As subjects
As researchers
Funding research
Helping in dissemination
The current newborn App
Researching the literature
Networking with other patient groups and being the voice of the patient on committees
Lobbying and working with the National Screening Committee
Health Innovation Challenge Fund