sickle cell disease: newborn screening in france and the uk - jacques elion

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)

[email protected]

GLOBAL GLOBIN 2020 CHALLENGEParis May 30-31, 2016

European Union27 countries population 510 millions

http://upload.wikimedia.org/wikipedia/commons/b/b7/Flag_of_Europe.svg

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


Programme standards for antenatal screening (2)

•All fathers of carrier women’s babies offered information, counselling and testing


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)


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)


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)


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



Haemoglobinopathy Screening Programme• Review of data on clinical care in UK

Overview



Haemoglobinopathy Screening Programme• Care programmes

Sickle Cell Disease in the UK

From Piel et al, Nat Genetics 2010

Overview




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




sickle cell disease: newborn screening in france and the uk - jacques elion

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