the view from europe professor helen dolk eurocat project leader eurocat central registry,...
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The View from Europe
Professor Helen DolkEUROCAT Project Leader
EUROCAT Central Registry, University of UlsterAnnual BINOCAR Meeting, Swansea
Cotober 2014
Central Registry Belfast
IRELANDDublin
South East IrelandCork & Kerry
Full Member
Associate Member
Size of Circle
< 10,000 births per year
10,000 - 40,000 births per year
>40,000 births per year
Map of EUROCAT Full and Associate Member Registries
BELGIUMAntwerp
Hainaut-Namur
FRANCEParis
StrasbourgRhone-Alps
Ile de la ReunionFrench West Indies
MALTA
FINLANDSWEDENNORWAY DENMARKOdense
UNITED KINGDOMWessex
Thames ValleyE Mid & S York
Northern EnglandSouth West England
Wales
PORTUGALSouth Portugal
NETHERLANDSNorthern Netherlands
ITALYEmilia Romagna
Tuscany
CROATIAZagreb
CZECH REPUBLIC
AUSTRIAStyria
UKRAINE
POLANDWielkopolska
SWITZERLANDVaud
GERMANYSaxony-Anhalt
Mainz
SPAINBasque CountryValencia RegionSpain Hospital
Network
HUNGARY
Why European Collaboration?
• Pooling of data
• Comparison of data between registries/countries
• Sharing of expertise
• Joint approach to European public health questions
• Sharing of resources (e.g. website, software)
History of EUROCAT
• Conceived in 1974, at a Workshop convened by the European Economic Community's Committee on Medicinal and Public Health Research to improve "the methodology of population studies throughout the Community". Congenital anomalies chosen as first topic for concerted action.
• EUROCAT established in 1979 as a prototype for European health surveillance aiming to assess the feasibility of pooling data across national boundaries, in terms of standardization of definitions, diagnosis and terminology and confidentiality. Central Registry in Department of Epidemiology, Catholic University of Louvain, Brussels.
• Michel Lechat 1927-2014
Co-founder of EUROCAT with Josephine Weatherall
Timeline 1979-2014 and beyond
Continued:
• 1991 transfers from “Research” to “Health Information”. Central Registry at Scientific Institute for Public Health, Brussels. Central Registry moved briefly to LSHTM, UK in 1999.
• 2000-2014 - Funded by EU DSanco as Rare Diseases activity, Central Registry at University of Ulster
• 2015 Central Registry will move to Joint Research Centre at ISPRA, Italy, under the EU Rare Diseases Platform.
Creation
•Population-based registries•Central Database and standard dataset
Expansion
•Expansion in Europe and Associate Members•Paper to electronic data
Systems
developme
nt
•EDMP software & electronic transmission•Website dissemination•Data Quality Indicators•Statistical Monitoring•Use of data for Research
Institution
al sustainabil
ity
•Separation of central functions and research?•Integration with other European institutions, systems and databases?
•Member State support?
What is a disease registry and is there an ideal size?
The bringing together of sources of expertise (people) and sources of data to shed light on a disease in relation to its prevalence, causes/prevention and care/services in a specified population
- expertise: different clinical areas, epidemiology, statistics, public health, specific exposure assessment fields ……….. and the expertise of those personally affected
- data sources- Electronic data sources present increasing opportunities, but also
challenges, across Europe- Registry = validated data
Regional (up to 40,000 births), national networking, European networking
Types of surveillance based on CA registries
• Statistical Monitoring (without prior hypothesis)– Recent Clusters in time– Trends in time, geographical differences
• Response to exposure incidents/health threats/disasters– Chernobyl– Swine Flu/H1NI
• Surveillance oriented to identifying environmental causes (with different levels of prior hypothesis)– Pharmacovigilance– Envirovigilance
• Surveillance oriented to evaluating primary prevention– NTD prevalence and prevention by periconceptional folic acid
• Surveillance oriented to health service needs and evaluation– Prenatal screening and diagnosis, TOPFA, mortality rates– Children needing services
.
Antiepileptic studies Literature review for signals
Test signals in Case-malformed control design for specificity
3.9 million births, 1995-2005
19 registries: pooling
Including TOPFA
Exposure data collected mainly prospectively in pregnancy
Epilepsy: 3 per 1,000 women, now AEDs used for other indications
To develop a European reproductive pharmacovigilance system • To develop and test an efficient and cost-effective system for safety evaluation of
drugs during pregnancy, based on EUROCAT registries combined with existing healthcare databases
– Signal detection and signal evaluation– Registry Linkage to prescription databases, exposed cohorts, population
databases– Designs: case-malformed control, cohort
• To quantify the risk of congenital anomalies related to four drug classes:– new antiepileptics,– insulin analogues,– anti-asthmatics,– Antidepressants (SSRIs)
• To develop a framework for evaluation of the efficacy of pregnancy-related drug safety measures including
– drug utilisation studies– monitoring the effectiveness of pregnancy prevention programmes (e.g.
isotretinoin)– a scoping study of the role of internet access to
drugs and related safety information by pregnant women
Antidepressant (SSRI) exposure in early pregnancy
• Aims: To examine the specificity of association between specific SSRIs and specific congenital anomalies
• Case-malformed control study
• Population: 12 EUROCAT registries , 1995-2009, 3.3 million births
• SSRI exposure among registrations 0.8%
• Cases: CHD, CHD subtypes, and other CA “signals” from the literature
• Controls: other CA (excl genetic syndromes)
• EUROCAT study Results:
• Severe CHD OR 1.56 (1.03-2.38)
• OR>2 for anorectal atresia&stenosis, gastroschisis, renal dysplasia, clubfoot
• Risks similar for all types of SSRI
• Interpretation: non-specific SSRI teratogenic effect? depression? Susceptibility to depression? Lifestyle confounders? Or more than one of these.
• EUROmediCAT: updating data to 2012, prescription data linkage where available, population cohort in 3 countries, drug utilisation study
Types of surveillance based on CA registries
• Statistical Monitoring (without prior hypothesis)– Recent Clusters in time/ clusters in space– Trends in time, geographical differences
• Response to exposure incidents/health threats/disasters– Chernobyl– Swine Flu/H1NI
• Surveillance oriented to identifying environmental causes (with different levels of hypothesis)– Pharmacovigilance– Envirovigilance
• Surveillance oriented to evaluating primary prevention– NTD prevalence and prevention by periconceptional folic acid
• Surveillance oriented to health service needs and evaluation– Prenatal screening and diagnosis, TOPFA, mortality rates– Children needing services
*
Prevalence per 10,000 births of Neural Tube Defects, for All Full Member Registries, from 1991 – 2010*Still births and Fetal Deaths from 20 weeks gestation
Has periconceptional folic acid supplementation in Europe prevented neural tube defects?
Primary Prevention of Congenital Anomalies
• EUROCAT in collaboration with EUROPLAN have developed recommendations on policies to be considered for the primary prevention of congenital anomalies in National Plans (and Strategies) on Rare Diseases– EUCERD approval– J Public Health Genomics 2014, Taruscio et al.
• In the field of:– Medicinal drugs– Food/nutrition and lifestyle (e.g. folic acid, obesity, smoking, alcohol)– Health Services (e.g. vaccination, women with chronic diseases, genetic
counselling)– Environmental pollution incl. the workplace
• Mechanisms:– Preconceptional care – high vs low risk parents– Health promotion to future parents and awareness raising: major health
determinants + pregnancy specific issues– Public health approaches: vaccination, food fortification– Regulatory policies (pharmaceutical, food, environmental, tobacco, alcohol)– Research and surveillance (CA and exposure), and expert review
Key Public Health Indicators for CA
2008-2012:
where is the UK?
Perinatal Mortality due to CABy Country 2008-2012
Aus
tria
Bel
gium
Cro
atia
Den
mar
k
Fra
nce
Ger
man
y
Hun
gary
Irel
and
Ital
y
Mal
ta
Net
herla
nds
Nor
way
Pol
and
Por
tuga
l
Spa
in
Sw
itzer
land
Ukr
aine UK
EU
RO
CA
T
0
0.5
1
1.5
2
2.5
3
3.5
4
1st week deaths
Fetal deaths
Rat
e p
er 1
,000
bir
ths
Prevalence of Prenatally Diagnosed CA By Country 2008-2012
Austri
a
Belgium
Croat
ia
Denm
ark
Franc
e
Germ
any
Hunga
ry
Irelan
dIta
lyM
alta
Nethe
rland
s
Norway
Poland
Portu
gal
Spain
Switzer
land
Ukrain
eUK
EUROCAT
0
5
10
15
20
25
30
35
40
Diag n/k
Not PD
PD non-chromo
PD chromo
Rat
e p
er 1
,000
bir
ths
Termination of Pregnancy for Fetal Anomaly By Country 2008-2012
Austri
a
Belgium
Croat
ia
Denm
ark
Franc
e
Germ
any
Hunga
ry
Irelan
dIta
lyM
alta
Nethe
rland
s
Norway
Poland
Portu
gal
Spain
Switzer
land
Ukrain
eUK
EUROCAT
0
1
2
3
4
5
6
7
8
9
Non-chromo
Chromosomal
Rat
e p
er 1
,000
bir
ths
Down Syndrome By Country 2008-2012(9% of all CA)
Au
stri
a
Be
lgiu
m
Cro
atia
De
nm
ark
Fra
nce
Ge
rma
ny
Hu
ng
ary
Ire
lan
d
Italy
Ma
lta
Ne
the
rla
nd
s
No
rwa
y
Po
lan
d
Po
rtu
ga
l
Sp
ain
Sw
itze
rla
nd
Ukr
ain
e
UK
EU
RO
CA
T
0
0.5
1
1.5
2
2.5
3
3.5
4
TOPFA
Fetal death
Live birth
Rat
e p
er 1
,000
bir
ths
Proportion of all births to mothers 35 years and older, 1990-99,2000-9.
Ukrain
e
Poland
: Wiel
kopo
lska
Malt
a
Germ
any
Austri
a: S
tyria
Denm
ark:
Ode
nse
Norway UK
Irelan
d
Franc
e
Switzer
land:
Vau
dSpa
in0.0
5.0
10.0
15.0
20.0
25.0
30.0
35.0
1990-99
2000-09
% m
oth
ers
35+
yea
rs
See Loane et al European Journal of Human Genetics 2013: Twenty-year trends in the prevalence of Down syndrome and other trisomies in Europe: impact of maternal age and prenatal screening.
Neural Tube Defects By Country 2008-2012(3.6% of all CA)
Aus
tria
Bel
gium
Cro
atia
Den
mar
k
Fra
nce
Ger
man
y
Hun
gary
Irel
and
Ital
y
Mal
ta
Net
herla
nds
Nor
way
Pol
and
Por
tuga
l
Spa
in
Sw
itzer
land
Ukr
aine UK
EU
RO
CA
T
0
0.5
1
1.5
2
2.5
3
3.5
4
TOPFA
Fetal death
Livebirth
Rat
e p
er 1
,000
bir
ths
Conclusions - 1
• Why European?– To pool, compare, and share people & resources
• Why CA Surveillance?– For prevention and care
• Why registers?– To bring the people (expertise of many kinds)
together with the data– TOPFA coverage essential
Conclusions - 2
– Why are not having more success preventing CA?• TOPFA are preventable too• Expectations• Preconceptional and interconceptional interventions
– Emerging issues:• Obesity and diabetes• Asthmatics/asthma and antidepressants/depression• Internet availability of teratogenic drugs
EUROCAT Registry LeadersProf. Martin Haeusler (Styria, Austria)Dr. Vera Nelen (Antwerp, Belgium)Prof. Christine Verellin-Dumoulin (Hainut, Belgium)Prof. Ingeborg Barisic (Zagreb, Croatia)Dr. Antonin Sipek (Czech Republic)Dr. Ester Garne (Odense, Denmark)Dr. Annukka Ritvanen (Finland)Dr. Babak Khoshood (Paris, France) Dr Bruno Schaub (French West Indies, France)Dr Hanitra Randrianaivo (Reunion, France)Dr. Annette Queisser-Luft (Mainz, Germany)Dr. Anke Rissmann (Saxony Anhalt, Germany)Dr. Judit Beres (Hungary)Dr. Robert McDonnell (Dublin, Ireland)Dr. Carmel Mullaney (SE Ireland)Dr. Mary O’Mahoney (Cork and Kerry, Ireland)Dr. Gioacchino Scarano (Campania, Italy)Prof. Elisa Calzolari (Emilia Romagna, Italy)Dr. Fabrizio Bianchi (Tuscany, Italy)Dr. Miriam Gatt (Malta)Dr. Ieve Grinfelde and Dr. Ivea Cirule (Latvia)Dr. Marian Bakker (N Netherlands)Prof. Marta Ebbing (Norway)Prof. Anna Latos-Bielenska (Wielkopolska, Poland)
Dr. Carlos Matias Dias (S Portugal)Dr Gorazd Rudolf (Slovenia)Dr. Larraitz Arriola (Basque Country, Spain)Prof. Maria-Luisa Martinez Frias (Spain Hospital Network)Dr. Oscar Zurriaga (Valencia, Spain)Dr Karin Kallen (Sweden)Dr. Marie-Claude Addor (Switzerland)Prof. Liz Draper (EMYSCAR, UK)Prof. Judith Rankin (N England, UK)Dr. Rosie Thompson (SW England, UK)Dr. Catherine Rounding (Thames Valley, UK)Mr David Tucker (Wales)Dr. Diana Wellesley (Wessex, UK)Prof Joan Morris (UK)Dr Wladimir Wertelecki (Ukraine) EUROCAT Central Registry (University of Ulster, UK)Prof. Helen DolkMs Maria LoaneMrs Ruth GreenleesMrs Barbara NortonDr. Nichola McCulloughDr. Breidge BoyleMrs Barbra WebberDr. Rhonda Curran
Percentage of births in population covered by EUROCAT registries 2011(should it be 100%? – quality vs quantity)
Austria (1F) 13%
Belgium (2F) 27%
Croatia (1F) 20%
Czech Republic (1A) 100%
Denmark (1F) 8%
Germany (2F) 3%
Ireland (3F) 62%
Spain (2F, 1A) 34%
Finland (1A) 100%
France (3F, 1A) 14%
Hungary (1F) 100%
Italy (2F) 14%
Malta (1F) 100%
Netherlands (1F) 10%
Norway (1F) 100%
Poland (1F, 1A) 100%
Portugal (1F) 19%
Sweden (1A) 100%
Switzerland (1F) 10%
United Kingdom (6F) 32%
Affilliates and applicants
Bulgaria
Cyprus
Greenland
Latvia
Moldova
Slovenia
EU countries not covered
Estonia, Greece, Lithuania, Luxembourg, Romania, Slovakia
Perinatal Mortality By Registry 2008-2012
Sty
ria
, Au
stri
a
An
twe
rp, B
elg
ium
Ha
ina
ut,
Be
lgiu
m
Za
gre
b, C
roa
tia
Od
en
se, D
en
ma
rk
Fre
nch
W In
die
s, F
ran
ce
Isle
de
la R
eu
nio
n, F
ran
ce
Pa
ris,
Fra
nce
Ma
inz,
Ge
rma
ny
Sa
xon
y A
nh
alt,
Ge
rma
ny
Hu
ng
ary
Co
rk a
nd
Ke
rry,
Ire
lan
d
Du
blin
, Ire
lan
d
S E
Ire
lan
d
Em
ilia
Ro
ma
gn
a, I
taly
Tu
sca
ny,
Ita
ly
Ma
lta
N N
eth
erl
an
ds
No
rwa
y
Wie
lko
po
lska
, Po
lan
d
S P
ort
ug
al
Ba
squ
e C
ou
ntr
y, S
pa
in
Va
len
cia
Re
gio
n, S
pa
in
Va
ud
, Sw
itze
rla
nd
Ukr
ain
e
E M
ids
& S
Yo
rks,
UK
N E
ng
lan
d, U
K
S W
En
gla
nd
, UK
Th
am
es
Va
lley,
UK
Wa
les,
UK
We
sse
x, U
K
EU
RO
CA
T
0
0.5
1
1.5
2
2.5
3
3.5
4
1st week deaths
Fetal deaths
Rat
e p
er 1
,000
bir
ths
Termination of Pregnancy for Fetal Anomaly By Registry 2008-2012
Sty
ria
, Au
stri
a
An
twe
rp, B
elg
ium
Ha
ina
ut,
Be
lgiu
m
Za
gre
b, C
roa
tia
Od
en
se, D
en
ma
rk
Fre
nch
W In
die
s, F
ran
ce
Isle
de
la R
eu
nio
n, F
ran
ce
Pa
ris,
Fra
nce
Ma
inz,
Ge
rma
ny
Sa
xon
y A
nh
alt,
Ge
rma
ny
Hu
ng
ary
Co
rk a
nd
Ke
rry,
Ire
lan
d
Du
blin
, Ire
lan
d
S E
Ire
lan
d
Em
ilia
Ro
ma
gn
a, I
taly
Tu
sca
ny,
Ita
ly
Ma
lta
N N
eth
erl
an
ds
No
rwa
y
Wie
lko
po
lska
, Po
lan
d
S P
ort
ug
al
Ba
squ
e C
ou
ntr
y, S
pa
in
Va
len
cia
Re
gio
n, S
pa
in
Va
ud
, Sw
itze
rla
nd
Ukr
ain
e
E M
ids
& S
Yo
rks,
UK
N E
ng
lan
d, U
K
S W
En
gla
nd
, UK
Th
am
es
Va
lley,
UK
Wa
les,
UK
We
sse
x, U
K
EU
RO
CA
T
0
2
4
6
8
10
12
Non-chromo
Chromosomal
Rat
e p
er 1
,000
bir
ths
Prenatal Diagnosis By Registry 2008-2012
Sty
ria
, Au
stri
a
An
twe
rp, B
elg
ium
Ha
ina
ut,
Be
lgiu
m
Za
gre
b, C
roa
tia
Od
en
se, D
en
ma
rk
Fre
nch
W In
die
s, F
ran
ce
Isle
de
la R
eu
nio
n, F
ran
ce
Pa
ris,
Fra
nce
Ma
inz,
Ge
rma
ny
Sa
xon
y A
nh
alt,
Ge
rma
ny
Hu
ng
ary
Co
rk a
nd
Ke
rry,
Ire
lan
d
Du
blin
, Ire
lan
d
S E
Ire
lan
d
Em
ilia
Ro
ma
gn
a, I
taly
Tu
sca
ny,
Ita
ly
Ma
lta
N N
eth
erl
an
ds
No
rwa
y
Wie
lko
po
lska
, Po
lan
d
S P
ort
ug
al
Ba
squ
e C
ou
ntr
y, S
pa
in
Va
len
cia
Re
gio
n, S
pa
in
Va
ud
, Sw
itze
rla
nd
Ukr
ain
e
E M
ids
& S
Yo
rks,
UK
N E
ng
lan
d, U
K
S W
En
gla
nd
, UK
Th
am
es
Va
lley,
UK
Wa
les,
UK
We
sse
x, U
K
EU
RO
CA
T
0
5
10
15
20
25
30
35
40
45
50
Diag n/k
Not PD
PD non-chromo
PD chromo
Rat
e p
er 1
,000
bir
ths
Down Syndrome By Registry 2008-2012
Sty
ria
, Au
stri
a
An
twe
rp, B
elg
ium
Ha
ina
ut,
Be
lgiu
m
Za
gre
b, C
roa
tia
Od
en
se, D
en
ma
rk
Fre
nch
W In
die
s, F
ran
ce
Isle
de
la R
eu
nio
n, F
ran
ce
Pa
ris,
Fra
nce
Ma
inz,
Ge
rma
ny
Sa
xon
y A
nh
alt,
Ge
rma
ny
Hu
ng
ary
Co
rk a
nd
Ke
rry,
Ire
lan
d
Du
blin
, Ire
lan
d
S E
Ire
lan
d
Em
ilia
Ro
ma
gn
a, I
taly
Tu
sca
ny,
Ita
ly
Ma
lta
N N
eth
erl
an
ds
No
rwa
y
Wie
lko
po
lska
, Po
lan
d
S P
ort
ug
al
Ba
squ
e C
ou
ntr
y, S
pa
in
Va
len
cia
Re
gio
n, S
pa
in
Va
ud
, Sw
itze
rla
nd
Ukr
ain
e
E M
ids
& S
Yo
rks,
UK
N E
ng
lan
d, U
K
S W
En
gla
nd
, UK
Th
am
es
Va
lley,
UK
Wa
les,
UK
We
sse
x, U
K
EU
RO
CA
T
0
0.5
1
1.5
2
2.5
3
3.5
4
4.5
5
TOPFA
Fetal death
Live birth
Rat
e p
er 1
,000
bir
ths
Anomalies Typically Requiring Surgery By Registry 2008-2012 (Excluding
Chromosomal Cases)S
tyri
a, A
ust
ria
An
twe
rp, B
elg
ium
Ha
ina
ut,
Be
lgiu
m
Za
gre
b, C
roa
tia
Od
en
se, D
en
ma
rk
Fre
nch
W In
die
s, F
ran
ce
Isle
de
la R
eu
nio
n, F
ran
ce
Pa
ris,
Fra
nce
Ma
inz,
Ge
rma
ny
Sa
xon
y A
nh
alt,
Ge
rma
ny
Hu
ng
ary
Co
rk a
nd
Ke
rry,
Ire
lan
d
Du
blin
, Ire
lan
d
S E
Ire
lan
d
Em
ilia
Ro
ma
gn
a, I
taly
Tu
sca
ny,
Ita
ly
Ma
lta
N N
eth
erl
an
ds
No
rwa
y
Wie
lko
po
lska
, Po
lan
d
S P
ort
ug
al
Ba
squ
e C
ou
ntr
y, S
pa
in
Va
len
cia
Re
gio
n, S
pa
in
Va
ud
, Sw
itze
rla
nd
Ukr
ain
e
E M
ids
& S
Yo
rks,
UK
N E
ng
lan
d, U
K
S W
En
gla
nd
, UK
Th
am
es
Va
lley,
UK
Wa
les,
UK
We
sse
x, U
K
EU
RO
CA
T
0
1
2
3
4
5
6
7
8
TOPFA
Fetal death
Livebirth
Rat
e p
er 1
,000
bir
ths
Neural Tube Defects By Registry 2008-2012
Sty
ria
, Au
stri
a
An
twe
rp, B
elg
ium
Ha
ina
ut,
Be
lgiu
m
Za
gre
b, C
roa
tia
Od
en
se, D
en
ma
rk
Fre
nch
W In
die
s, F
ran
ce
Isle
de
la R
eu
nio
n, F
ran
ce
Pa
ris,
Fra
nce
Ma
inz,
Ge
rma
ny
Sa
xon
y A
nh
alt,
Ge
rma
ny
Hu
ng
ary
Co
rk a
nd
Ke
rry,
Ire
lan
d
Du
blin
, Ire
lan
d
S E
Ire
lan
d
Em
ilia
Ro
ma
gn
a, I
taly
Tu
sca
ny,
Ita
ly
Ma
lta
N N
eth
erl
an
ds
No
rwa
y
Wie
lko
po
lska
, Po
lan
d
S P
ort
ug
al
Ba
squ
e C
ou
ntr
y, S
pa
in
Va
len
cia
Re
gio
n, S
pa
in
Va
ud
, Sw
itze
rla
nd
Ukr
ain
e
E M
ids
& S
Yo
rks,
UK
N E
ng
lan
d, U
K
S W
En
gla
nd
, UK
Th
am
es
Va
lley,
UK
Wa
les,
UK
We
sse
x, U
K
EU
RO
CA
T
0
0.5
1
1.5
2
2.5
TOPFA
Fetal death
Livebirth
Rat
e p
er 1
,000
bir
ths
Types of surveillance based on CA registries
• Statistical Monitoring (without prior hypothesis)– Recent Clusters in time– Trends in time, geographical differences
Cluster output: Scan method
Cluster detection for the period 2007-2013 by year: no. EUROCAT registries included in monitoring and their population coverage, number of tests conducted and clusters detected, and results of cluster investigations.
2007 2008 2009 2010 2011 2012 2013 Total 2007-2013
Registries (n) 10 11 10 16 16 17 18 -
Annual population covered (no. births)
234,317
226,011
272,975
390,510
401,282
473,675
505,250 -
Cases of Congenital Anomaly (n) 11,891 10,687 12,048 16,654 18,275 22,152 23,619 -
Congenital anomaly subgroups (n) 75 75 75 76 76 73 72 -
Tests performed (n) 482 500 487 766 805 882 901 4823
Cluster detection rate (%) 2.90% 3.40% 4.72% 3.92% 2.48% 3.06% 3.77% 3.42%
Total clusters detected (n)
14
17
23
30
20
27
34
165
New* clusters (n) 12 15 18 21† 16 24 20 126
Old* clusters (n) 2 2 4 4 3 3 7 25
Continuing* Cluster (n) 0 0 1 5 1 0 7 14
Investigation results (new clusters only)
Cluster confirmed, no explanation 2 9 6 7 2 11 7 44 (34.9%)
Cluster due to data quality issues 3 3 5 6 2 6 10 34 (27.8%)
Cluster due to increasing prenatal diagnosis
0 0 2 1 7 0 0 10 (7.9%)
Heterogeneous anomalies in cluster
4 3 2 3 5 6 3 26 (20.6%)
No investigation 3 0 3 4 0 1 0 11 (8.7%)
Anomalies Typically Requiring Surgery By Country 2008-2012 (Excl Chrom)
20% of all CA, half of all cases needing surgery
Aus
tria
Bel
gium
Cro
atia
Den
mar
k
Fra
nce
Ger
man
y
Hun
gary
Irel
and
Ital
y
Mal
ta
Net
herla
nds
Nor
way
Pol
and
Por
tuga
l
Spa
in
Sw
itzer
land
Ukr
aine UK
EU
RO
CA
T
0
1
2
3
4
5
6
7
8
9
TOPFA
Fetal death
Livebirth
Rat
e p
er 1
,000
bir
ths
Overview:2008-2012
Types of surveillance based on CA registries
• Statistical Monitoring (without prior hypothesis)– Recent Clusters in time– Trends in time, geographical differences
• Response to exposure incidents/health threats/disasters– Chernobyl– Swine Flu/H1NI
Pandemic influenza studies
• Time series study– January 2007 – March 2011 conceptions– 26,976 non-chromosomal congenital anomaly registrations from 10 European
countries
• Exposure based on country-specific influenza season data from WHO-EuroFlu influenza season tables
EUROCAT CA case delivery
TimelineGestational age
is subtracted
LMP
CorrespondingCA-specific
Critical Period
A fortnightIs added
Conception