Sickle Cell Disease: Newborn screening in France and the UK
Jacques Elion, MD, PhD
French National Reference Centers for Sickle Cell Disease
Department of Medical Genetics and Inserm UMR 1134
Robert Debré Mother and Child University Hospital, 75019 Paris, FranceGuadeloupe University Hospital, 97139 Les Abymes (French West Indies)
GLOBAL GLOBIN 2020 CHALLENGEParis May 30-31, 2016
European Union27 countries population 510 millions
French AntillesGuadeloupeMartinique
French Guianapopulation 1 million
Réunion & Mayoteislands
population 1 million
European Unionpopulation 490 millions
EU ultraperipheral regions
Azores, Madeira &Canarias islands
population 2,5 millions
In Europe, SCD is both:
- endogenousGreeceSouthern Italy (Sicily…)Portugal
- exogenous with populations originating fromAfrica or the Carribean islandsMiddle East and the Arabic peninsulaIndian sub-continent
… SCD is not only a disease of black populations!
Royaume Uni Pays-Bas
Espagne
Portugal
Belgique
AllemagneFrance
Italie
Grèce
Irlande
Luxembourg
Danemark
Norvège
Suède
Finlande
βS
Caribbean and French Guiana
African immigration
Trends in at-risk populations (% pop)
1988 / 2006
Adapted from Modell et al, Scan J Clin Lab Invest 2007; 67: 39-70
European Union27 countries population 510 millions
France and the UK:
Highest absolute nb of patients
≈ 15.000 SCD patients/each
Most frequent
genetic disease
Geographical distribution of SCD in England: NHR registrations by 2016
26
102
85
256030
34
53
6
9
38 20
92
88
14
55 20
1545
RéunionGuyaneMayotteGuadeloupeMartinique
49
46
192
10 years of NBS for SCD in France
Incidence1/1881
Paris 1/814
Guiana 1/196
Haemoglobinopathy NBS in the UK
• National Health Service-1941
• National Haemoglobinopathy Screening Programme - 2001
• Centralised commissioning of Specialised Haemoglobinopathy Services 2008
Global care for SCD in France
• Social Security - 1945
• National Sickle Cell Disease NBS Screening Program - (1989) 2000
• Reference/Competence Centres 2005 Ntnl Rare Disease Program
• Comprehensive Health Networks for Rare Diseases 2014
Filières de Santé – Maladies rares
Global care for SCD in France
• Social Security - 1945
• National Sickle Cell Disease NBS Screening Program - (1989) 2000
• Reference/Competence Centres 2005 Ntnl Rare Disease Program
• Comprehensive Health Networks for Rare Diseases 2014
Filières de Santé – Maladies rares
targetted to the newborns at risk
26 5,52%
10213,75%
85 15,65%
256062,97%
30 14,88%34 18,33%
53 31,20%
6 19,74%
9 16,28%
38 30,59% 2041,62%
9243,20%
88 11,23%
14 21,71%
55 17,71%2019,12%
1545
81,40%
RéunionGuyaneMayotteGuadeloupeMartinique
49 22,48%
46 14,47%
19231,49%
10 years of NBS for SCD in France
Targetting 2000 → 2010
19,1% → 31,5%
Courtesy of Béatrice Gulbis
SCD Genotypes NBS in the Parisian area
(cumulative results 2000-2010)
0
100
200
300
400
500
600
700
800
2001 2002 2003 2004 2005 2006 2007 2008 2009 2010
SS
SS (ou) Sb°ThalSb°Thal
Sb+Thal
SC
S/E
S/D punjab
A/S antilles
AS ou Sb+Thal
S/PHHF
Linked antenatal and neonatal haemoglobinopathy screening programme (UK): 2001
Aims:
•To support people to make informed choices during pregnancy and before conception •To improve infant health through prompt identification of affected babies •To provide high quality and accessible care throughout England •To promote greater understanding and awareness of the disorders and the value of screening
Programme standards: Antenatal screening
• All pregnant women offered screening by 10wks gestation
• All fathers of carrier women’s babies offered information, counselling and testing
• 50% of all prenatal diagnoses to be performed by 12 weeks and six days of gestation
Programme standards: Antenatal screening
• All pregnant women offered screening by 10wks gestation (in France Pilot programs)
• All fathers of carrier women’s babies offered information, counselling and testing
• 50% of all prenatal diagnoses to be performed by 12 weeks and six days of gestation
Programme standards for antenatal screening (UK)
•Pregnant women should be tested before 10 wks gestation
National Haemoglobinopathy Screening Programme Data report 2013-14
National Haemoglobinopathy Register (UK)
• About 75% of patients registered
• National data on treatment (hydroxyurea/transfusion/BMT)
• Reporting of SAE’s
• Annual review
National Haemoglobinopathy Register (UK)
• About 75% of patients registered
• National data on treatment (hydroxyurea/transfusion/BMT)
• Reporting of SAE’s
• Annual review
In France: - National registry for thalassaemias (since 2010) - no National SCD Registry yet (should start in 2017)
Sickle Cell and Thalassaemia
Data Report 2013/14 Trends and performance analysis
Programme standards for antenatal screening (3)
• 50% of all prenatal diagnoses to be performed before 13 weeks
National Haemoglobinopathy Screening Programme Data report 2013-14
Programme standards for antenatal screening (2)
•All fathers of carrier women’s babies offered information, counselling and testing
National Haemoglobinopathy Screening Programme Data report 2013-14
Newborn Outcomes Project (March 2016)
Evaluation of Linked Antenatal and Newborn Sickle Cell and Thalassaemia Screening
Programmes
Sickle Cell and Thalassaemia
sct.screening.nhs.uk
Newborn Outcomes Project
Main aims of the programme:
Are babies seen in clinic by three months of age?
Are babies prescribed penicillin by three months of age?
Is the screening test confirmed?
Overall mortality/are any deaths < 5 years sickle cell related?
Review completeness and accuracy of the mothers antenatal screening results
Overview of Babies Registered: Sept 1st 2010 – Dec 31st 2015
Table 1: All babies registered (n = 1788)
N
Sickle Cell 1378
Thalassaemia 142
Unconfirmed 37
Migrated 62
Insignificant 150
Born Abroad 19
Overview of Sickle Cell Cases
Table 2: Confirmed cases in follow-up, (n = 1378)
Data In Follow-up (%)
Seen 1351 (98.0)
≤ 100 days 1170 (86.6)
101 ≤ 130 days 94 (6.9)
131 ≤ 160 days 36 (2.7)
> 160 days 51 (3.8)
Overview of Sickle Cell Cases
Table 3: Distribution of confirmed cases, (n = 1378)
Diagnosis N (%) In Follow-up (%)
SS 885 (64.2) 868 (98.1)
SC 386 (28.0) 378 (97.9)
S/β+thal 68 (4.9) 68 (100.0)
S/β⁰thal 8 (0.6) 8 (100.0)
S/δthal 2 (0.1) 2 (100.0)
S/HPFH 23 (1.7) 22 (95.7)
S/Dpunjab 2 (0.1) 1 (50.0)
S/E 3 (0.2) 3 (100.0)
S/Lepore 1 (0.1) 1 (100.0)
Overview of Sickle Cell Cases
Table 4: Geographical location of confirmed cases, (n = 1378)
Centre N (%) In Follow-up (%)
Birmingham 96 (7.0) 95 (99.0)
Bristol 22 (1.6) 21 (95.5)
Cambridge 6 (0.4) 6 (100.0)
Leeds 37 (2.8) 37 (100.0)
Liverpool 9 (0.6) 9 (100.0)
London 998 (72.4) 973 (7.5)
Manchester 62 (4.5) 62 (100.0)
Newcastle 8 (0.6) 8 (100.0)
Oxford 60 (4.3) 60 (100.0)
Sheffield 70 (5.1) 70 (100.0)
Southampton 10 (0.7) 10 (100.0)
Overview of Sickle Cell Cases
Table 5: Ethnic Origin of confirmed cases, (n = 1378)
Ethnicity N (%)
African 972 (70.5)
Asian 4 (0.3)
Black (other) 83 (6.0)
Caribbean 143 (10.4)
Indian 10 (0.7)
Mixed (black) 45 (3.3)
Mixed (other) 24 (1.7)
Pakistani 2 (0.1)
Other 17 (1.2)
White 13 (0.9)
Unknown 65 (4.7)
Overview of Mortality
Deaths due to complications of SCD occurred after 1st year of life
1.3 deaths per 1000 years follow-up
0.1 death per 100 children affected
Standard met
Overview
• Epidemiology of SCD in UK• Highlights in developing healthcare services
for SCD in England• Review of current data from National
Haemoglobinopathy Screening Programme• Care for SCD in the UK
Evolution of national programme for clinical care
– Specialised service definition for central commissioning of services 2008
– Regional specialist centres and clinical networks
– Published guidelines and and key performance indicators
– Peer review of Specialist centres
Audit Standards for Sickle
• Pneumococcal vaccination
• Oral penicillin V prophylaxis
• Annual transcranial doppler screening age 3-16
• Retention under follow-up
Standards for the
Clinical Care ofAdults
with Sickle Cell Disease
in the UK
2008
CareBook.qxd:Layout 1 2 /7/08 09:03 Page 2
Improving survival in childhoodQuinn et al, Blood 2010
Complication rate E.London neonatal cohort. Telfer et al, Haemtologica 2007
Causes of death in adults with SCD
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Platt et al, 1994. N=209 Powars et al, 2005.N=186
Perronne et al, 2002.N=61
NCPOD 2008. N= 40
Not known
Unrelated tosickle
suddenly athome
Perioperative
Chronic organdamage
CVA
Acute infection
Acute vaso-occlusive
National Confidential Enquiry into Patient Outcome and Death: 2008
19 deaths in cases admitted in pain
• Excessive opiates in 9
• Overdose leading to death in 5
• No assessment of pain and opiate adverse effects in 13
Potential risk factors for early mortality in England
• Substandard medical care
• Poor transitional care
• Lost to follow-up
• Psychosocial problems
• Low socioeconomic status
National Peer Review of Specialist Centres2008 Paediatric; 2013: Adult; 2015: Paediatric and adult
• Gradual improvements in meeting standards
• Data collection is a problem
• Insufficient staff numbers
• Patients not always engaged or satisfied with aspects of services
Conclusions
• SCD is a very common inherited condition in UK
• It is almost entirely restricted to ethnic minority groups
• There has been a gradual evolution in national services for SCD
• Care within the NHS can be considered comprehensive
• There a still challenges for achieving and maintaining high quality care.
Thank you very much!Merci!
Acknowledgements: Rupa Sisodia (Newborn Outcomes Project)
sct.screening.nhs.uk
Comprehensive care programme for Sickle Cell Disease in the UK
Dr Paul TelferSenior Lecturer in Haematology, Barts and The London School of
Medicine, Queen Mary University of London
Consultant Paediatric and Adult Haematologist, Royal London Hospital, Barts Health NHS Trust
Overview
• Epidemiology of SCD in UK• Highlights in developing healthcare services
for SCD in England• Review of current data from National
Haemoglobinopathy Screening Programme• Review of data on clinical care in UK
Overview
• Epidemiology of SCD in UK• Highlights in developing healthcare services
for SCD in England• Review of current data from National
Haemoglobinopathy Screening Programme• Care programmes
Sickle Cell Disease in the UK
From Piel et al, Nat Genetics 2010
Overview
• Epidemiology of SCD in UK• Highlights in developing healthcare services
for SCD in England• Review of current data from National
Haemoglobinopathy Screening Programme• Care programmes
National Health Service Act 1946
• Services provided free at the point of use
• Services financed from central taxation
• Everyone eligible for care (even people temporarily resident or visiting the country).
Overview
• Epidemiology of SCD in UK• Highlights in developing healthcare services
for SCD in England• Review of current data from National
Haemoglobinopathy Screening Programme• Care programmes