eurocat: surveillance of environmental impact
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EUROCAT: Surveillance of Environmental Impact. Dr Martine Vrijheid (Lyon, France) for EUROCAT Prof Helen Dolk, University of Ulster WHO Collaborating Centre for the Epidemiological Surveillance of Congenital Anomalies - PowerPoint PPT PresentationTRANSCRIPT
EUROCAT: Surveillance of EUROCAT: Surveillance of Environmental ImpactEnvironmental Impact
Dr Martine Vrijheid (Lyon, France) for
EUROCAT
Prof Helen Dolk, University of Ulster
WHO Collaborating Centre for the Epidemiological Surveillance of Congenital Anomalies
Supported by the EU-Commission Public Health Directorate Programme of Community Action on Rare Diseases
AREHNA, Kos, 9-11 June 2005
EUROCAT: Surveillance of EUROCAT: Surveillance of environmental impactenvironmental impact
• What is EUROCAT?
• Environmental causes of congenital anomalies
• What is surveillance?
• Approaches to surveillance of environmental impacts in causation of congenital anomalies
1. Routine monitoring
2. Detection and response to temporal and spatial clusters
3. Evaluation of specific hypotheses
• Conclusions
AREHNA, Kos, 9-11 June 2005
What is EUROCAT?What is EUROCAT?
• European network of registries for the epidemiologic surveillance of congenital anomalies.
• Started in 1979
• More than 1 million births surveyed per year in Europe (25% of European birth population)
• 40 registries in 19 countries of Europe
• Standardised database on >350,000 cases of congenital anomaly among livebirths, stillbirths and terminations of pregnancy since 1980 – updated annually
AREHNA, Kos, 9-11 June 2005
EUROCAT RegistriesEUROCAT Registries
• European network of population-based registries for the epidemiologic surveillance of congenital anomalies.
• Started in 1979
• More than 1 million births surveyed per year in Europe
• 40 registries in 19 countries of Europe
• Standardised database on >350,000 cases of congenital anomaly among livebirths, stillbirths and terminations of pregnancy since 1980 – updated annually
AREHNA, Kos, 9-11 June 2005
EUROCATEUROCAT
•Objectives
To provide essential epidemiologic information on congenital anomalies in Europe
To facilitate the early warning of teratogenic exposures
To act as an information and resource centre for the population and health professionals regarding clusters or exposures or risk factors of concern
To provide a ready collaborative network and infrastructure for research related to the causes and prevention of congenital anomalies
AREHNA, Kos, 9-11 June 2005
EUROCATEUROCAT
•Registries provide high data quality:
Population-based
Multiple sources of ascertainment
Follow-up cases for diagnostic information
Ascertain anomalies diagnosed after the early neonatal period
Ascertain terminations of pregnancy following prenatal diagnosis
•Quality at the expense of completeness of geographical coverage
AREHNA, Kos, 9-11 June 2005
Environmental causes : Potential Environmental causes : Potential adverse outcomes of embryonic/fetal adverse outcomes of embryonic/fetal exposureexposure
• Congenital anomalies (2-4% of births)congenital heart disease 25%
limb anomaly 17%
central nervous system anomaly
(e.g. neural tube defects incl spina bifida) 9%
cleft palate or cleft lip 6%
chromosomal syndrome (incl Down Syndrome) 12%
• Spontaneous abortion (15% of recognized pregnancies) or stillbirth (<1% of births)
• Low birthweight (6-7% of births) – preterm and/or growth retarded in utero
• Poor neurodevelopmental outcomes, including motor, cognitive and behavioural outcomes
• Effects later in childhood/ adult life (cancer, fertility, etc)
AREHNA, Kos, 9-11 June 2005
Environmental causes of Environmental causes of congenital anomalies: 3 important congenital anomalies: 3 important principlesprinciples
• Susceptibility to an environmental agent (and type of effect) depends on the developmental stage at the time of exposure (“sensitive period”) Before pregnancy recognized (later for other
outcomes)
• The effect of an environmental agent increases in frequency and degree as dosage increases and there may be a practical “threshold” dose
• Susceptibility to an environmental agent depends on the background of other genetic and environmental factors
AREHNA, Kos, 9-11 June 2005
Environmental pollution as a Environmental pollution as a cause of congenital anomalies?cause of congenital anomalies?
• Disasters/accidental or deliberate high exposure incidents: Radiation: Hiroshima – microcephaly, mental retardation Methylmercury: Minamata – cerebral palsy PCB contaminated oil: Taiwan, Japan –skin, nail, teeth,
growth, neurodevelopment
• Chronic exposures: Water disinfection/chlorination byproducts? Residence near (hazardous) waste landfill sites?? Endocrine disrupting chemicals?? Pesticides?
Dolk & Vrijheid 2004EUROCAT Special Report “A review of Environmental Risk
Factors for Congenital Anomalies” www.eurocat.ulster.ac.uk/pubdata
AREHNA, Kos, 9-11 June 2005
Public Health SurveillancePublic Health Surveillance
• The continuous scrutiny of the distribution of disease in a population in order to take and evaluate control measures.
• As opposed to epidemiologic research, tends to be (Thacker and Berkelman 1988)
Problem detection/hypothesis generating rather than hypothesis testing
Ongoing, using routine data collection systems, with minimal often incomplete data as opposed to time limited, tailored, extensive and complete data collection
Simple and descriptive analysis with timely and targeted communication to agencies involved with policy and intervention, as opposed to complex analysis with sporadic communication to clinical or academic audience
AREHNA, Kos, 9-11 June 2005
EUROCAT Approaches to EUROCAT Approaches to SurveillanceSurveillance
1. Routine monitoring of temporal trends
2. Detection and response to temporal and spatial clusters
3. Evaluation of specific hypotheses
AREHNA, Kos, 9-11 June 2005
1. Routine monitoring1. Routine monitoring
• EUROCAT Reports / web
• Effects of folic acid supplementation on trends in neural tube defects throughout Europe;
• Reports of rising prevalence of hypospadias;
• Increasing prevalence of gastroschisis.
AREHNA, Kos, 9-11 June 2005
Trends in the prevalence of congenital anomalies per 10,000 births: all and cardiac anomalies, all EUROCAT registries combined, 1980-2002
0
50
100
150
200
250
1980-84
1985-89
1990-94
1995-99
2000-02
CardiacLB+SB+TOPAll anomalies LB
All anomaliesLB+SB+TOP
AREHNA, Kos, 9-11 June 2005
NTD Prevalence per 10,000 NTD Prevalence per 10,000 births 1980-2001 (LB + SB + births 1980-2001 (LB + SB + TOP)TOP)
NTD rate by year in the UK and Ireland: adjusted for registry
year1980 1982 1984 1986 1988 1990 1992 1994 1996 1998 2000 2002
0
10
20
30
40
50
NTD rate by year in Europe: adjusted for registry
year1980 1982 1984 1986 1988 1990 1992 1994 1996 1998 2000 2002
0
10
20
30
40
50
UK and Ireland Continental Europe
AREHNA, Kos, 9-11 June 2005
Hypospadias Prevalence Rates by Year of Birth in England and Wales, 1964-1996 (NCAS Data)
0
0.2
0.4
0.6
0.8
1
1.2
1.4
1.6
1.8
2
64 66 68 70 72 74 76 78 80 82 84 86 88 90 92 94 96
Year of birth
pre
vale
nce
pe
r 1
,00
0 b
irth
s
This study
Matlai and Beral
Implementation of guideline to exclude glanular cases
AREHNA, Kos, 9-11 June 2005
Gastroschisis per 10,000 births, all European registers combined, 1980-2002
0
0.5
1
1.5
2
2.5
1980-84
1985-89
1990-94
1995-99
2000-02
Gastroschisis
AREHNA, Kos, 9-11 June 2005
2. 2. Detection and response to Detection and response to temporal and spatial clusterstemporal and spatial clusters
Clusters arising through surveillance Cluster concerns from local community
• Routine statistical monitoring to detect temporal clusters carried out by EUROCAT;
• Empirical investigations:• geographic heterogeneity of congenital anomalies in the
UK• Geographical clustering of anophthalmia in England;
• EUROCAT Cluster Advisory Service: www.eurocat.ulster.ac.uk.
AREHNA, Kos, 9-11 June 2005
Clusters under random Clusters under random patternpattern
AREHNA, Kos, 9-11 June 2005
Routine Statistical Routine Statistical MonitoringMonitoring
• Statistical tests for detection of clusters Eg. Kulldorf techniques, adjusting for multiple testing: scan moving window
• Would routine detection of clusters overwhelm our capacity to respond?
• Main problems are not random variation, but ascertainment variation Lack of sensitivity in picking up exposure related
variation
AREHNA, Kos, 9-11 June 2005
Empirical clustering Empirical clustering observationsobservations
Anophthalmia in England (Dolk 98)• 444 cases born 1988-94, prevalence 1.0 per
10,000 births
• “Clustering” consistent with random distribution
Geographical variation in congenital anomalies in Britain (Dolk 2003)
• 5 regions over 9 year period
• 6,959 non-chromosomal anomalies; 1611 Down syndrome cases.
• “Clustering” consistent with random variation
AREHNA, Kos, 9-11 June 2005
3. 3. Evaluation of specific Evaluation of specific environmental exposure environmental exposure hypotheseshypotheses
Chernobyl• Conclusion: no detectable effect of Chernobyl on
overall prevalence of congenital anomalies in Europe (Dolk 1999)
Hazardous Waste Landfill Sites• Population covered approx 100,000 births within 7
km of 26 hazardous waste landfill sites in seven regions
• 1089 non-chromosomal cases, 270 chromosomal cases, 2508 controls
• Residence within 3 km vs 3-7 km
• Non-chromosomal anomalies OR 1.33 (95%CI 1.11-1.59) near sites (Dolk, Vrijheid 1998);
• Chromosomal anomalies OR 1.41 (95%CI 1.00-1.99) (Vrijheid, Dolk, 2002)
AREHNA, Kos, 9-11 June 2005
Evaluation of specific Evaluation of specific environmental exposure environmental exposure hypotheseshypotheses
Risk of hypospadias in relation to maternal occupational exposures to endocrine disrupting chemicals
• Routine data UK-NCAS, 1980-96
• Includes code for maternal occupation at time of birth registration
• Job-exposure matrix to classify exposure to potential EDCs (van Tongeren 2002): 7 chemical groups (phthalates, pesticides, alkyl phenolics, heavy metals, etc); 8% of cases classified with probable exposure
• Results: (Vrijheid, Armstrong et al 2003)• No increase in risk of hypospadias in categories of “possible” or
“probably” exposure to EDCs
• Increased risk for hair dressers / exposure to phthalates in one time period, before adjustment for socio-economic status
AREHNA, Kos, 9-11 June 2005
Evaluation of specific Evaluation of specific environmental exposure environmental exposure hypotheseshypotheses
• Will we be overwhelmed with associations with environmental pollution beyond our capacity to respond?
Missing what is real: Exposure misclassification tends to dilute real associations
Finding what is not real: Ascertainment variation and confounding can exaggerate or reduce real associations or produce spurious associations where none exists
AREHNA, Kos, 9-11 June 2005
Advantages of congenital anomaly Advantages of congenital anomaly surveillancesurveillance
• Short time lapse between exposure and diagnosis
• Continuously updated (spatially referenced) denominator statistics (births)
• Network of established registers with harmonised data collection
AREHNA, Kos, 9-11 June 2005
Methodological challenges in Methodological challenges in environmental surveillanceenvironmental surveillance
Relating to congenital anomaly data: Classification: lumping and splitting Adjustment for terminations of pregnancy Diagnostic and ascertainment variation
Relating to other data sources: Easily accessible systems of georeferencing of cases and
births across Europe Easily accessible information on environmental exposures
in Europe How to defined “similar” exposures?: lumping and splitting
again Exposure modelling/exposure surrogates/biomarkers?
Easily accessible information on socioeconomic status across Europe
Integration of systems, including expertise
AREHNA, Kos, 9-11 June 2005
ConclusionsConclusions
Fetal life is an especially sensitive period to environmental exposures
Crucial fetal exposure occurs before the pregnancy is recognized
The proportion of congenital anomalies attributable to environmental pollution may not be high, but any excess cases would represent a failure of our environmental health protection system
EUROCAT, covering a quarter of European births, can play an important part in a European environmental health surveillance strategy