Tài liệu THE BURDEN OF DISEASE ATTRIBUTABLE TO ENVIRONMENTAL POLLUTION pptx

Substantial proportions of global disease burden are attributable to these major risks where developing countries bear the greatest burden, unsafe water and indoor air pollution are the

THE BURDEN OF DISEASE ATTRIBUTABLE TO ENVIRONMENTAL POLLUTION

Professor Ian Mathews and Dr Sharon Parry

Department of Epidemiology, Statistics, Public Health

University of Wales College of Medicine

Summary

This paper presents a summary of the information available in the literature aimed at estimating the fraction of mortality and/or morbidity that can be attributed to environmental factors It is a first step in the process of quantifying the possible burden

of disease from environmental pollution Current estimates are based on very uncertain data and limited datasets and therefore need to be interpreted with extreme caution

The extent to which environmental pollutants contribute to common diseases is not accurately resolved However, global estimates conservatively attribute about 8-9% of the total burden of disease to pollution Data is presented on the evidence available for diseases such as asthma, allergies, cancer, neuro-developmental disorders, congenital malformations, effects of ambient air pollution on birth weight, respiratory and cardiovascular diseases and mesothelioma Health effects from environmental lead exposure and disruption of the endocrine function are also presented

1 Background

The need to estimate the burden of disease associated with pollutants is highlighted not only by the evidence base on associations but also by the scale of use of chemicals in our modern society Fifteen thousand chemicals are produced in quantities in excess of 10,000 pounds annually and 2,800 are produced in annual quantities in excess of 1 million pounds These high volume chemicals have the greatest potential to be dispersed in environmental media and less than half of these have been tested for human toxicity (US EPA, 1996; Goldman LR et al, 2000; NAS, 1984) There are approximately 30,000 chemicals in common use and less than 1% of these have been subject to assessment of toxicity and health risk (Royal Commission on Environmental Pollution, 2003)

Environmental pollutants may be defined as chemical substances of human origin in air, water, soil, food or the home environment The extent to which such pollutants may contribute to common diseases of multi-factorial aetiology is not accurately resolved However in recent years attempts have been made to estimate the environmentally attributable burden of disease globally, in the USA and in regions of Europe In the first instance estimation has concentrated on health outcomes for which there is strong evidence of an association with pollutants

At a global level a summary of early estimates first appeared in the 1997 report ‘Health and Environment in Sustainable Development’ by the World Health Organisation (WHO, 1997) In subsequent years further estimates have been made of the fraction of mortality and morbidity that can be attributed to environmental factors (Smith KR et al, 1999; Ezzati M et al, 2002) Substantial proportions of global disease burden are attributable to these major risks where developing countries bear the greatest burden, unsafe water and indoor air pollution are the major sources of exposure and children under five years of age seem to bear the largest environmental burden Estimates vary

but conservatively about 8-9% of the total disease burden may be attributed to pollution (Briggs D, 2003)

In the framework of the European Environment and Health Strategy various Technical Working Groups on priority diseases reviewed the evidence base in support of the development of the Children’s Environment and Health Action Plan for the European region (CEHAPE) expressed in the Budapest declaration (WHO 2004a) It was considered that one sixth of the total burden of disease from birth

to 18 years is accounted for by exposure to contaminated air, food, soil and water causing respiratory diseases, birth defects, neuro-developmental disorders and gastrointestinal disorders Waterborne gastrointestinal disorders are not a major public health problem in the UK The remaining priority diseases identified by CEHAPE are considered below for children

In Section 2 two different methodologies are outlined by which burden of disease attributable to environment can be estimated In the first the health loss due to environmental risk factor(s) is calculated as a time-indexed “stream” of disease burden due to a time-indexed “stream” of exposure Such a time-indexed “stream” of exposure data is only available for environmental lead and ambient urban outdoor air pollution Therefore in Section 9 WHO estimates of the burden of disease attributable to environmental lead exposure are presented Similarly in section 10 and 11 estimates are given of the burden of disease due to exposure to air pollution published by the Committee on the Medical Effects of Air Pollution of the Department of Health

Since population exposure data are lacking in connection with asthma, cancer and neurobehavioral disorders a second methodology is employed in Sections 3, 5 and 6 This was devised in the U.S specifically for children and is outlined in Section 2 This method is also used to infer the burden of allergy attributable to environment in Section 4

Finally the primary research literature was assessed to estimate the burden of congenital malformations attributable to environment (Section 7) as well as effects of ambient air pollution on birth weight (Section 8) and on children’s lung function (Section 10)

2 Methodology

The Global Burden of Disease (GBD) 1990 project stimulated debate about the crucial role of risk factor assessment as a cornerstone of the evidence base for public health action It was affected by a lack of conceptual and methodological comparability across risk factors but the Comparative Risk Assessment (CRA) project co-ordinated by WHO was planned as one of the outputs of the GBD 2000 project to strengthen these aspects (WHO 2004b) In particular in the CRA framework:

• The burden of disease due to the observed exposure distribution in a population is compared with the burden from a hypothetical distribution or

series of distributions, rather than a single reference level such as the exposed population

non-• The health loss due to risk factor(s) is calculated as a time-indexed

“stream” of disease burden due to a time-indexed “stream” of exposure

• The burden of disease and injury is converted into a summary measure of population health, which allows comparing fatal and non-fatal outcomes, also taking into account severity and duration

The CRA framework has been used to investigate the burden of disease associated with exposure to a limited number of environmental risk factors These are: unsafe water, sanitation and hygiene, urban air pollution and indoor air pollution from household use of solid fuels as well as lead exposure (WHO 2004c)

To provide the knowledge base for the development of the Children’s Environment and Health Action Plan for the European region (CEHAPE), the burden of disease attributable to environmental factors (BODAE) was assessed in terms of deaths and disability-adjusted life years (DALYS) among children and adolescents The assessment was restricted to outdoor and indoor air pollution, inadequate water and sanitation and lead (Valent F et al, 2004) The methodology employed is outlined in Appendix 1 and used the distribution of risk-factor exposure within the study population and the exposure-response relation for the risk factor to calculate the impact fraction for the particular health outcome

To date the estimates of burden of disease attributable to environmental factors provided by the WHO are of limited value in a UK context with the exception of lead exposure Inadequate water and sanitation and indoor air pollution from household use

of solid fuel for cooking and heating are not major issues in the UK Further the population health effects arising from outdoor ambient air pollution have been estimated

by the Committee on the Medical Effects of Air Pollution (COMEAP) of the Department

of Health (COMEAP 1998)

However, a different methodology has been developed and employed in the USA to estimate the morbidity and mortality for asthma, cancer and developmental disabilities in children (Landrigan P.J et al 2002) For each disease, expert panels were convened from prominent physicians and scientists with extensive research publication in the field Each panel member was supplied with an extensive collection of reprints of published articles that discussed linkages between the disease in question and toxic environmental exposures A formal decision-making process, the modified Delphi technique (Fink A 1984), was then enacted by which the panel developed a best estimate from 0% to 100% of the Environmentally Attributable Fraction (EAF) for the disease in which they were expert Panels chose deliberately not to consider outcomes related to tobacco or alcohol that are the consequence, at least in part, of personal or familial choice It is these EAF’s which are used below in estimating the BODAE for the

population of children in England and Wales for asthma, cancer and developmental disabilities

3 Asthma

3.1 Evidence of environmental aetiology

It is reasonable to assume that the variations in asthma prevalence are largely attributable to environmental factors Although genetic differences could contribute to the geographical pattern, it seems very unlikely that they could account for the great variation that is found within Europe, and they obviously do not explain the time trends

In children and young adults, asthma usually involves an allergic reaction to inhaled allergens The simplest explanation of variations in prevalence would be a corresponding variation in exposure to the principal allergens The house dust mite is the source of the allergen to which asthmatic patients are most commonly sensitive The changes in asthma prevalence have therefore been ascribed to increased exposure to house dust mites, consequent upon changes within houses such as more fitted carpets and better insulation But in fact there is little evidence that exposure to mites has risen, apart from one study

The effects of air pollution on children’s health has been reviewed (WHO, 2005) and it is considered that air pollution exacerbates symptoms of asthma and that the respiratory health of children, especially those with asthma, will benefit substantially from a reduction in air pollution especially that from motor vehicle exhausts Some air pollutants (diesel particulates) appear to potentiate the effects of airborne allergens There is little evidence for a causal association between prevalence/incidence of asthma and air pollution There is some (rather inconsistent) evidence that asthma prevalence

is related to the proximity of peoples’ residence to roads (Maynard RL, 2001) Asthma attacks can certainly be provoked by episodes of acute air pollution

Most people spend most of their time indoors, so the quality of indoor air is probably more important than that of outdoor air Oxides of nitrogen are produced by gas cookers and in some studies (though not in others) have been associated with respiratory symptoms (Hasselblad V et al, 1992) There is some evidence that asthma is associated with formaldehyde and other volatile organic compounds in the home(Krzyzanowski M et al, 1990; Hosein HR et al, 1989)or school(Smedie G et al, 1997)environment These compounds are emitted by various sources used in furniture, hobbies and other indoor activities; they may act as respiratory irritants or increase the risk of allergy as represented by serum IgE levels In numerous surveys, indoor mould growth and dampness have been associated with respiratory symptoms (Burr ML, 2001) Environmental tobacco smoke (passive smoking) increases a child’s risk of respiratory illness, and smoking during pregnancy has adverse effects on the lungs of the unborn child There is some uncertainty as to whether smoking (active or passive) actually causes asthma, partly depending on how the disease is defined It may be the case that it aggravates rather than causes it(Strachan DP et al, 1998)

3.2 Burden of disease

Asthma is a common disease Although its mortality is fairly low, it gives rise to a great deal of anxiety, particularly in childhood, when it is a major cause of hospital admission and morbidity The peak incidence is in the first five years of life, though the disease can start at any age The prevalence declines at adolescence, when remissions tend to exceed incidence, but relapse often occurs during adult life after a symptom-free interval It is sometimes difficult to distinguish asthma from other common conditions, such as respiratory infections in infants and chronic obstructive pulmonary disease in later adult life If asthma is defined more narrowly in some surveys than in others, large differences in prevalence can be created quite artificially Nevertheless, a useful body of data has been produced by numerous surveys that have used similar methods, and some fairly consistent patterns are now emerging

The International Study of Asthma and Allergies in Childhood (ISAAC, 1998) was conducted in 155 centres within 56 countries and the prevalence of wheeze in the last

12 months in 13-14 year olds was 29-32% in the UK The European Community Respiratory Health Survey (ECRHS) was conducted in 48 centres within 22 countries, mostly in Western Europe (Janson C et al, 2001) It showed a similar pattern to that found by ISAAC The prevalence of specific IgE, a marker of atopic sensitivity, which is known to be associated with asthma was much higher in UK than in Iceland, Greece, Norway, Italy and parts of Spain

Wherever a survey has been repeated after an interval of 10 years or more, in the same area using the same methods, the prevalence of asthma has been found to have risen Most of these surveys have used questionnaires enquiring about symptoms (particularly wheeze) rather than asthma alone, so the increase is not merely attributable to a change in diagnostic fashion

One of these (in South Wales) used an exercise challenge test and from 1973 to 1988 asthma prevalence increased, as measured by symptoms and exercise challenge (Burr

ML et al, 1989) A repeat survey in 2003 (unpublished) suggests that a further rise has occurred in symptoms but not in the response to exercise The consistency with which increases have been reported from all parts of the world is remarkable Some support for a true increase is also provided by increases in related diseases such as allergic rhinitis and eczema (although the data are largely derived from questionnaires); successive surveys in Japan have shown a rise in the prevalence of specific IgE in serum(Nakagomi T et al, 1994)

The Welsh Health Survey recorded that in 2003/2004 10% of adults (aged over 16 years) and 12% of children reported that they were currently being treated for asthma and 1% of children reported that they were currently being treated for other respiratory conditions (Welsh Health Survey, 2003) The Health Survey for England (2002) reported rates of doctor diagnosed asthma of 20.5% in 0-15 year olds and 14.5% for all ages

The burden of disease registered in Primary Care is recorded by 371 practices across the UK submitting data to the General Practice Research database The prevalence of asthma in different age groups is shown below

Prevalence of treated asthma per 1000 patients

For Males (1998)

0-4

years 5-15 years 16-24 years 25-34 years 35-44 years 45-54 years 55-64 years 65-74 years 75-84 years 85+ years

crude rate (all years)

age standardised rate (all years) rate per

16-24 years

25-34 years

35-44 years

45-54 years

55-64 years

65-74 years

75-84 years

85+

years

crude rate (all years)

age standardised rate (all years) rate per

Some information is available as part of the Hospital Episode Statistics detailing episodes of admitted patient treatment delivered by NHS hospitals in England The most recent data is available for the 2003/2004 financial year when 63,949 episodes of unspecified asthma (ICD10: J45.9) and 9,228 episodes of status asthmaticus (ICD10: J46.X), 60 episodes of nonallergenic asthma (ICD10: J45.1), 26 cases of mixed asthma (ICD10: J45.8), were recorded

3.3 Burden of Asthma attributable to Environment

3.3.1 Asthma attributable to outdoor non-biologic pollution

The expert US panel on asthma considered only outdoor non-biologic pollutants from sources potentially amenable to abatement such as vehicular exhausts and emissions from stationary sources Using this definition the panel estimated that 30% of acute exacerbations of childhood asthma (range 10-35%) are environmentally related (Landrigan PJ et al, 2002) Applying this EAF to national survey data, Primary Care data and data on hospital inpatient episodes gives:

Total Population ▲

Prevalence rate

EAF BODAE

Number of children in England and Wales aged 10-14 years

with wheeze in last 12 months 3425023 29.0% 30% 297977Number of children in England and Wales aged 0-9 years

with wheeze in last 12 months

6401995 29.0% 30% 556974 Number of children in England and Wales aged 0-15 years

currently being treated for asthma

10488736 12.0% 30% 377594 Number of children in England and Wales aged 0-15 years

with doctor diagnosed asthma

10488736 20.5% 30% 645057 Number of adults in England and Wales aged 16 and over

currently being treated for asthma 41553180 10.0% 30% 1246595Number of adults in England and Wales aged 16 and over

with doctor diagnosed asthma

41553180 14.5% 30% 1807563

▲ Source: Census 2001 data

(i) ISAAC survey data was for 13 to 14 year olds so it is assumed that the prevalence of wheeze in 10-12 year olds is the same

(ii) Assuming the same prevalence in 0-10 year olds as in 12-13 year olds

Environmentally attributable prevalence of treated asthma per 1,000 patients in Primary Care

Inpatient episodes in NHS hospitals in England in 2003/2004

Unspecified asthma ICD10:J45.9 63949 x 30% = 19185

Status asthmaticus ICD10:J46.X 9228 x 30% = 2768

Nonallergenic asthma ICD10:J45.1 60 x 30% = 18

3.2.2 Proportion of asthma attributable to indoor biologic pollution

There is strong evidence linking asthma exacerbations to derp 1 allergen indoors and relatively strong evidence linking asthma exacerbations to contamination of the indoor environment with moulds Survey data demonstrates that 95% of asthmatics have derp 1 concentrations in their mattress dust in excess of WHO guideline value of 2 µg/g-1 Survey data also demonstrates that approximately 17% of homes are contaminated with mould Since most people spend more than 90% of their time indoors there is significant exposure of the asthmatic population to these allergens Although no estimates of EAF from these sources are available it is likely to be of similar magnitude to that due to outdoor non biologic sources

3.4 Conclusion

The burden of asthma exacerbations attributable to non-biologic air pollution is considerable Asthma exacerbations can be measured by the prevalence of wheeze in the last 12 months and prevalence of current treatment for asthma Using UK data on such prevalence and the EAF cited above the burden of asthma exacerbations attributable to non-biologic pollution can be estimated This is 855,000 of those children reporting wheeze in the last twelve months and 378,000 of those children currently being treated for asthma as well as approximately one and a quarter million of those adults currently reporting being treated for asthma and 22,000 of inpatient episodes per annum

The epidemiological evidence base linking asthma exacerbations to indoor allergens such as der p1 and moulds is no less strong than that relating asthma to non-biologic outdoor air pollution It is, therefore, likely that the EAF used to obtain the above estimates could be doubled to give a more realistic estimate of the burden of asthma exacerbations attributable to environmental factors

4 ALLERGY

4.1 Evidence of environmental aetiology

The term allergy describes those immune responses that are potentially harmful to the host but which are directed against external agents that in themselves are not particularly harmful to us Many individuals synthesise specific IgE antibodies against

common environmental allergens, and they are termed atopic For example, grass or

tree pollens or nickel jewellery are indeed foreign material but pose no threat to us when

we come into contact with them However many individuals mount an immunological reaction to such structures which results in inflammation at the site of contact with the

allergen and hence symptoms and disease

The targets against which most allergic diseases are directed (i.e the allergens themselves – house dust mite, cat, grass pollens etc) are not becoming particularly more prevalent but the level of sensitization to them in the general population is The change in the biologic response to them is thought to reflect the effects of unidentified factors (possibly dietary fats and air pollutants) involved in the process of sensitization which occur at the level of the antigen presenting cell – T cell interaction in each individual

There would appear to be an increase in the numbers of the general population exposed

to some allergens, and possibly in their levels of exposures to some of these materials

1 As consumers: toothpastes, household sprays, cleaning materials, perfumes

2 Indoor environmental agents: e.g volatile organic compounds

3 Outdoor pollutants: diesel exhaust fumes

4.2 Burden of allergic disease

Up to 35% of the population demonstrate evidence upon testing of IgE immunological reactivity to allergens, a high proportion of whom (5-10% of the population) show clinical

features of one or more allergic disorders (most commonly asthma, eczema or hay

Welsh Health Survey (2003) show that 11% of children report skin complaints Health Survey for England (2001) data show that the rate of doctor diagnosed eczema was 13% for all ages in 2001:

4.3 Burden of allergic disease attributable to environment

There is no evidence on the EAF for allergic disease If it is assumed that the

exposures and mechanisms involved in the aetiology and exacerbation of asthma are

similar to those involved in allergy, then the EAF for asthma (i.e 30%), the percent of

children with skin complaints (11%) and of adults with allergic rhinitis (10%), may be

used to infer the BODAE for allergy

Allergic rhinitis (Total population of Eng & Wales) 52,041,916 x 10% x 30% = 1,561,257

Skin complaints (Population of children) 10,488,736 x 11% x 30% = 346,128

4.4 Conclusion

Environmental factors may be responsible for one and a half million cases of allergic

rhinitis and one third of a million cases of skin complaints in children

5 CANCER

Monozygotic and dizygotic twins have been studied in an attempt to apportion the

relative importance of genes and environment in the aetiology of cancer (Ahlbom A, et al

1997, Verkasalo PK 1999, Lichtenstein P et al 2000) The largest dataset used for

family studies is the nationwide Swedish Family – Cancer Database with more than

700,000 cancers and a population of 9.6 million Modelling of this data gave estimates

that environment has a principal causative role in cancer at all studied sites except for

thyroid (Czene K 2002)

5.2 Burden of disease and Burden of disease attributable to Environment

To assess the environmentally attributable fraction of childhood cancer an expert panel

was convened in the US in paediatric oncology, epidemiology and environmental

medicine The panel considered that extra genetic factors, defined broadly, caused

80-90% of cancers but noted that the specific causes of childhood cancer are largely

unknown It concluded that insufficient evidence exists to assign a best estimate of the

fraction of childhood cancer specifically attributable to toxic chemicals in the

environment (Robinson LL 1995) It agreed that the correct EAF would be in the range

5 to 90% (Landrigan PJ 2002) Therefore in calculating the environmental burden of

disease for childhood cancer for England and Wales the lowest estimate of 5% has

been used below

Since Adult occupational exposure to chemicals, cigarette smoking and alcohol

consumption are prevalent confounders to environmental exposure, no attempt has

been made to quantify the BODAE for adult cancers

Common Childhood (0-14 years) Cancers in England and Wales (2001)

6 Neuro-developmental disorders

6A Attention Deficit Hyperactivity Disorder (ADHD)

6A.1 Evidence of environmental aetiology

For all complex diseases, there is increasing evidence that genes may operate by influencing sensitivity to environmental risk factors There have been more than 14 twin studies across the world that have shown that ADHD is highly heritable with reported heritability estimates of between 60% and 91% (Thapar et al, 1999; Thapar 2002) Finally adoption studies have also shown increased rates of ADHD amongst biological but not adopted relatives of individuals affected by ADHD (Thapar, 2002) Most interest

to date has focussed on examining variants within genes coding for enzymes and proteins in the dopamine neurotransmitter system Association of a variant in the dopamine D4 receptor gene (the 7 repeat allele of a 48 bp VNTR) with ADHD has been widely replicated and shown to be significantly in a meta analysis of 14 studies (Faraone

et al, 2001)

There has been increased interest in gene-environment interaction effects in childhood psychopathology To date there have been virtually no published studies examining the co-action and interaction of genes and environment in ADHD However, preliminary findings from one study suggest interaction between a dopamine transporter gene variant (previously found to be associated with ADHD) and smoking in pregnancy (Kahn

et al, 2003)

Moreover, several studies have found a dose-response relationship between the number of cigarettes smoked in pregnancy and ADHD symptom scores in offspring (Linnet et al, 2003) There have been fewer studies examining the association of alcohol and drug use in pregnancy and ADHD and the evidence for association is mixed (Linnet et al, 2003) There is evidence that exposure to PCBs in utero (resulting from maternal ingestion of food contaminated with PCBs) may damage the child’s developing nervous system and produce intelligence and behavioural deficits such as inattention (Jacobson & Jacobson, 1996)

Ingestion of lead by children is known to lead to adverse neurocognitive consequences, specifically lowered IQ (Schwartz 1994) Some studies have suggested an association

of lead levels and ADHD symptoms (Tuthill, 1996) but it is not clear that exposure to lead is an important risk factor for the clinical diagnosis of ADHD

There is some evidence that head injury maybe associated with ADHD (Gerring et al, 1998) but other studies have not found such an association (Max et al 1997) Moreover, head injury appears to be associated with a range of behavioural problems rather than showing a specific relationship with ADHD and the evidence of an association between head injury and adverse cognitive and psychiatric sequelae is more compelling for severe rather than mild head injury (Goodman, 2002)

6A.2 Burden of disease

Attention Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder that is only diagnosed if the child meets stringent diagnostic criteria Two main diagnostic schemes are used in psychiatry, the International Classification of Diseases (ICD; WHO, 1993), more often used in Europe and the DSM (American Psychiatric Press, 1994) from the United States The diagnostic criteria in the current versions of the classification systems are similar although DSM-IV ADHD remains a more broadly defined category than ICD-10 Hyperkinetic disorder

The key features of ADHD are early onset, significant symptoms of inattention, impulsiveness and over activity These symptoms need to be developmentally inappropriate and associated with functional impairment (for example educational failure, peer difficulties) Both ICD-10 and DSM-IV also require that the symptoms (or impairment) are pervasive, that is occur in different settings (typically home and school) Evidence of brain dysfunction in individuals with ADHD has been found in cerebral imaging studies including functional MRI (Magnetic Resonance Imaging), PET (Positron Emission Tomography) and SPECT (single photon computed emission tomography) studies (Overmeyer et al, 2000, Volkow et al, 2001) A recent well designed controlled study published in the Journal of the American Medical Association reported clear evidence that drug naive children with ADHD had decreased grey and white matter volume and significantly smaller cerebellar volume compared to control children (Castellanos et al, 2002) Many of these neurobiological studies have suggested involvement of the prefrontal cortex and basal ganglia and there has been considerable

interest in dopaminergic neurotransmitter system (Zametkin & Liotto 1998) but it is clear that the neurobiological basis of ADHD is complex with involvement of many pathways

The prevalence of ADHD has been estimated at between 2 % and 5% (Faraone & Wilens, 2003) although prevalence figures vary according to the diagnostic criteria used (Costello et al 1996; Barkley, 1998) For Hyperkinetic Disorder, prevalence rates in the

UK have varied between 0.5% (for boys only) (Taylor et al, 1991) to 1.4% in the most recent UK survey (Meltzer et al, 2000) ADHD is much commoner in boys with a 3:1 sex ratio found in epidemiological studies and an even higher sex ratio in referred samples (Taylor et al, 1991; Barkley, 1998) Childhood ADHD frequently persists into adolescence with many symptoms of the disorder continuing into adulthood (Barkley, 1998; Manuzza et al, 1998) although it is not clear how many continue to meet full diagnostic criteria and whether current diagnostic criteria are appropriate for adults Increased rates of subsequent difficulties with employment, antisocial behaviour, driving offences, increased rates of criminal activity, as well as substance abuse have been noted (Barkley, 1998; Farrington et al, 1990)

There is considerable evidence for both under - and over diagnosis of ADHD in clinical practice (Thapar & Thapar, 2003) In the UK, only around 50% of children with HKD are recognised as having the disorder (Ford et al, 2003) and those referred show increased rates of co morbid psychiatric conditions and family adversity (Woodward et al, 1997)

To date, there is no convincing evidence of recent, increased prevalence rates of ADHD from UK epidemiological studies

6A.3 Burden of ADHD attributable to Environment

An expert committee convened by the US National Academy of Sciences (NAS) estimated in 2000 that 3% of neurobehavioural disorders in American children are caused directly by toxic environmental exposures and that another 25% are caused by interactions between environmental factors, defined broadly, and genetic susceptibility

of individual children (NAS, 2000) The authors of this paper consider this study the most authoritative published estimate of the EAF for these disorders and therefore have relied on the NAS estimate Of the total 28% of neurobehavioral disorders thought by the NAS committee to be caused wholly or partly by environmental factors, it was estimated that 10% (range 5-20%) are at least partly caused by toxic exposures, not including alcohol, tobacco, or drugs of abuse Using this information, the BODAE for England and Wales can be estimated as follows:

* in England and Wales (Census 2001)

** in England and Wales

6B Autism

Autism is now commonly regarded as belonging to a group of neurodevelopmental disorders that are sometimes called pervasive developmental disorders These are childhood onset conditions but problems nearly always persist into adulthood The key clinical features of autism include:

• onset in early childhood (some type of abnormality by 36 months of age)

• communication problems (both comprehension and expression and gesture as well

6B.1 Evidence of Environmental aetiology

Twin studies have shown that autism is highly heritable with a heritability of liability of greater than 90%, which is higher than other genetically influenced multifactorial neuropsychiatric disorders (Folstein & Rutter 1977; Bailey et al 1995) These family and twin studies also show that genetic factors do not entirely account for autism and that autism appears to be aetiologically as well as phenotypically heterogeneous There is also evidence that non genetic factors play an important role in influencing the

phenotypic manifestation of autism, in that there appears to be as much variability in

symptom expression within monozygote twin pairs as between monozygote pairs

(LeCouteur et al, 1996)

Whole genome linkage scans based on samples of multiply affected relatives are

beginning to yield significant findings thereby highlighting chromosomal regions that may

harbour susceptibility genes The most widely replicated region of linkage is on

chromosome 7q (Thapar & Scourfield, 2002) However the identification of a

susceptibility gene variant within this region and others chromosomal regions of interest

is awaited

Exposure to heavy metals in utero has also been suggested as a risk factor (Edelson &

Cantor, 1998) with recent interest in maternal dietary intake of fish during pregnancy

6B.2 Burden of disease

There is an extremely wide variation in the reported rates of autism Rates between

0.007 and 0.21% have been reported A recent authoritative review gave the median

prevalence rate as 0.1% (Fombonne, 2003) Just as for attention deficit hyperactivity

disorder (ADHD) the disorder is much commoner in boys than in girls (ratio 3:1) but it is

not known why this is the case (Rutter et al, 2003)

An increased prevalence rate over time has been reported with studies between 1966

and 1991 reporting an average prevalence of 0.044% and studies between 1992 and

2001 reporting an average prevalence of 0.127% (Volkmar et al, 2004)

In the only instance where prevalence rates were derived from successive birth cohorts

no statistically significant changes in prevalence rates of the disorder were found

(although the relatively low prevalence rates found in these 2 studies have raised some

concern that cases may have been missed (Volkmar et al., 2004)

6B.3 Burden of Autism attributable to Environment

* in England and Wales (Census 2001)

** in England and Wales

• Deficits in social functioning or adaptive behaviour (basic everyday skills) which are present from childhood

‘Significant impairment of intelligence’, is usually defined as an intellectual quotient (IQ) score more than two standard deviations below the general population mean (British Psychological Society, 2000) This means an IQ below 70 on recognised IQ tests such

as the Adult Intelligence Scale (Wechsler D, 1998) or the Intelligence Scale for Children (Wechsler D, 1992)

6C.1 Evidence of environmental aetiology

Biological, social and environmental factors are involved in causing learning disabilities Biological causes include genetic factors (e.g Downs syndrome), antenatal factors (e.g lead intoxication), perinatal factors (e.g birth asphyxia) and postnatal factors (e.g injury)

Between one in five and one in three children with severe learning disabilities have no identifiable biological cause

6C.2 Burden of disease

Studies across North America, Europe and Australia typically use IQ assessments to classify persons as having mild (IQ 50 or 55 to 70) or severe (IQ <50 or 55) learning disabilities Comprehensive reviews of the literature indicate that the overall prevalence rate for severe learning disabilities is between 3 and 4 people per 1,000 population This gives between 230,000 and 350,000 people in the UK with severe learning difficulties

Studies of mild learning disabilities have reported between less than 10 and 25-30 people per 1,000 population which suggests that between 580,000 and 1,750,000 people in the UK have a mild learning disability

The latest figures (2002/2003) for children on the social services register of children with learning disabilities in Wales are 2805

The Welsh Assembly Government collates information on children in education with special educational needs including those with a formal statement of special need See table below for numbers

The UK education system uses the term ‘learning difficulties’, rather than ‘learning disabilities’ The Warnock Committee proposed that the term ‘learning difficulties’ be defined as:

• A greater difficulty in learning than the majority of children of the same age

• A disability which prevents or hinders the child from making use of ordinary educational facilities

They suggested that about one in five children would have a learning difficulty at some time in their lives, arising, for example, from medical problems, sensory impairments, physical disabilities, emotional and behavioural difficulties, language impairments, specific learning problems (such as dyslexia), autism or pervasive learning difficulties

Pupils (of any age) with statements in schools, by type of school and need (Source

Statistical Directorate, 2004)

Primary Secondary Special All Pupils with a special need but no statement:

47,335 27,289 74,624

Moderate learning difficulties 18,519 9,842 28,361

Severe learning difficulties 458 57 515

Profound & multiple learning difficulties 33 1 34

Specific learning difficulties 3,891 4,223 8,114

Autistic Spectrum Disorders 245 57 302

Physical disabilities 358 236 594

Multiple sensory impairment 19 8 27

Speech, language & communication 4,017 521 4,538

Emotional & behavioral difficulties 3,437 4,010 7,447

Medical difficulties 384 158 542

Pupils with a statement of special need: 5,817 6,350 3,752 15,919

Moderate learning difficulties 1,464 2,124 680 4,268

Severe learning difficulties 427 280 1,239 1,946

Profound & multiple learning difficulties 152 38 519 709

Specific learning difficulties 485 1,465 15 1,965

Autistic Spectrum Disorders 452 185 526 1,163

Speech, language & communication 1,087 396 104 1,587

Emotional & behavioral difficulties 606 634 524 1,764

(adults)

* in England and Wales (Census 2001); ** in England and Wales

6.4 Conclusion

In children, approximately 133,000 cases of learning difficulty, 14,000 cases of ADHD and 1000 cases of Autism may be attributable to environmental factors However, these estimates are very rough and should be treated with caution

7 CONGENITAL ABNORMALITIES

7.1 Evidence for environmental aetiology

A large study in the UK revealed that 80% of the UK population reside within 2 Km of a landfill site (Elliot P, et al 2001) and that the relative risk of a congenitally malformed baby for mothers in this region in proximity was 1.01 Similar studies in Europe (Dolk H,

et al 1998) and Wales (Palmer SR et al, 2005; Nix B, et al 2005) give relative risk estimates of 1.33, 1.39 and 1.19 respectively Therefore by assuming that the increase

is due to environmental factors and if this was the only environmentally attributable risk (a conservative estimate) the EAF may be chosen at a mid-range value of the above relative risk estimates (i.e 1.20)

7.2 Burden of disease

The following outlines the incidence and outcome for selected congenital anomalies in the Welsh population recorded by the Congenital Anomaly Register and Information Service (CARIS)

Con Mals 1998-2003 Wales

Congenital Malformation

Cases (n)

Gross rate(all cases)/10,000 live&still births

Upper Limb reduction defects 147 8

Lower Limb reduction defects 76 4

Complex Cyanotic Disease (CHD) 134 7

Transpositional great vessels 79 4

Ventricual septal defects (VSD) 945 50

Atrioventicual septal defects (AVSD) 113 6

trisomy 21 - Down syndrome 377 20

trisomy 18 - Edwards syndrome 89 5

trisomy 13 - Patau syndrome 53 3

other chromosome anomalies 157 8

7.3 Burden of congenital malformations attributable to environment

Assuming that the observed increased risk in proximity to landfill sites is due to environmental factors and using an EAF of 0.2 then the burden attributable to environment would be a gross rate of 86 per 10,000 live and still births

8 Effects on birth weight of ambient air pollution

Birth-weights for babies born in Wales between 1983 and 1997 indicate that at 32 weeks gestation around 20% are born at a very low birth weight (<1500g) and around 95% are born at a low birth weight (< 2,500g) At 36 weeks gestation less than 3% are born at very low birth weight and around 25% are born at low birth weight At 40 weeks less

than 3% of babies are born below 2500g (Welsh Child Health System All births in Wales 1983-1997)

In a population-based case control study in the United States the combined effect on very low birth rate (<1,500g) of SO2 and total suspended particle (TSP) levels was analysed, using annual exposure estimates [Rogers et al 2000] Results showed that for babies born to mothers who were exposed to concentrations of the combined pollutants above the 95th percentile of the exposure distribution (56.8 g/m3), the relative risk was 2.88 (95% Confidence Interval; CI 1.16-7.13) Another study carried out in the United States has found similar result – the authors examined the association between PM10and birth weight in northern Nevada between 1991 and 1999, and found that a 10µg/m3increase in mean PM10 concentrations during the third trimester of pregnancy was associated with a reduction in birth weight of 11g (95% CI 2.3-19.8) [Chen et al 2002] A European study carried out in the Czech Republic examined the relationship between low birth weight, premature birth, and ambient TSP during each trimester in 108,000 singleton live births [Bobak 2000] The effects of these adverse birth outcomes were marginally stronger for exposures during the first trimester Adjusted odds ratios of low birth rate and prematurity were 1.15 (95% CI 1.07-1.24) and 1.18 (95% CI 1.05-1.31) for

a 50µg/m3 increase in TSP respectively In contrast, Landgren who studied the effects of air pollution on delivery of 38,000 Swedish women in 1985-1990 [Landgren 1996], and Maisonet et al who studied the effects of PM10 in live births born in six northeastern cities of the United States [Maisonet et al 2001], both showed results with no indication

of a positive association between prenatal exposure to particulate air pollution and low birth weight

8.1 Conclusion

To date, only a limited amount of epidemiological evidence has been collected and the results are equivocal

9 Environmental lead exposure

9.1 Exposure to environmental lead

Lead is distributed in the environment via industrial and vehicular emissions, house paint and plumbing As a result lead is present in air, dust, soil and water and the general population are exposed primarily via ingestion and inhalation (Valent et al., 2004)

Some of these exposures involve large sectors of the population (e.g industrial activity, use of lead in vehicle fuel) whilst others are more locally (lead water pipes) or culturally (lead in ceramic food containers) specific (Fewtrell et al 2004) In the UK, policies reducing exposure by leaded petrol and house paints has increased the relative impact

of other sources namely food and beverages (crops grown in soils of high lead content, food in soldered tins) (Moore et al 1979) and water (lead piping) (Watt et al 1996) The release of lead to air in the UK has considerably reduced following the ban on lead additives in petrol in the 1990s However, lead is still present in soil as a result of

deposition (particles falling to the ground or washed out by rain) from previous vehicular emissions, old leaded paint and landfill (EPAQS, 1998)

9.2 Measurements of exposure

The bulk of the human data on exposure to environmental lead are expressed in terms

of internal exposure, in particular blood lead levels Internationally, most biomonitoring studies, have been episodic rather than part of routine surveillance and are most commonly conducted on populations at risk due to their occupation or vicinity to a highly contaminated site (ATSDR, 1999)

However, blood lead levels in England were recorded in a sample of the population between April-June and between September-December 1995 A multi-stage stratified probability sampling design was used as part of the Health Survey for England to obtain representative data For subjects aged over 11 years, a geometric mean blood lead level of 2.0 µg/dl was recorded Blood lead levels were higher in males than females, increased with age and were highest in adults having higher consumptions of cigarettes and alcohol No differences between urban and non-urban populations were identified (Institute for Environment and Health, 1998)

Despite differences in methodology between this and previous UK surveys, blood lead levels appeared to have fallen since the 1984-1987 period (Delves et al 1996) with a long term downward trend of around 4% per year (DoE, 1988)

The Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC) included a measurement of blood lead levels in 584 two year old children in 1994 so that future follow up could assess the impact of lead exposure on their IQ Levels ranged from 0.8

to 27.6 µg/dl with a geometric mean of 3.44 µg/dl Children of younger mothers, children exposed to environmental tobacco smoke, children with pets in the home, children living close to higher levels of traffic and children who were not breast fed had statistically significantly higher blood lead levels Furthermore, children living in inner city areas had the highest levels whilst those living in outer areas had the lowest levels (Golding et al., 1996; Institute for Environment and Health, 1998)

9.3 Health effects

At high levels of exposure (blood lead level > 60µg/dl) acute effects are recorded ranging from gastrointestinal problems, lethargy and irritability, encephalopathy and death Chronic low level toxicity can remain asymptomatic However, in infants and young children the developing brain is particularly vulnerable and blood lead levels as low as 10 µg/dl or less can cause neurological deficits (Needleman and Gastonis, 1990; Canfield et al 2003)

Milder disease outcomes, in particular hypertension in adults and the loss of IQ points and the resultant increase in mild mental retardation (MMR) in children are of increasing concern at levels of exposure that were previously considered safe (ATSDR 1999)

9.4 Burden of disease

The World Health Organisation has assessed the disease burden from lead exposure for the year 2000 at global level, categorised by geographic region using the ‘exposure-based approach’ (WHO/ILO, 1998) The disease burden has been calculated by evaluating the population exposure distributions based on recorded blood lead levels in combination with estimates of disease rates (Fewtrell et al 2004)

Geometric mean and standard deviation blood lead levels were obtained for individual countries using population exposure data identified through a literature search Occupational exposures and studies of ‘hotspots’ were excluded Countries were grouped into 14 WHO regions (WHO, 2002) WHO European Region A includes the

UK Separate levels were compiled for children and adults where data was available Two health outcomes were considered

9.4.1 Loss of IQ points and increase in mild mental retardation (MMR)

This was based on a linear relationship between blood lead levels and loss of IQ points established by a meta-analysis of cross sectional and longitudinal studies (Schwartz 1994) A loss of 1.3 IQ points per 5 µg/dL blood lead interval for blood lead levels between 5 and 20 µg/dL was assumed MMR was defined as having an IQ score of between 50 and 69 and estimates were calculated using the ratio of those who already had a low IQ score and for whom a loss of a few points would result in them being categorised as having MMR

Using studies from 6 European Region A countries (which did not include any studies from the UK) the mean blood level for urban children was 3.5 µg/dl and the mean blood level for urban adults was 3.7 µg/dl It was calculated that for Region A, 227 people per

1000 population had a loss of 0.65 IQ points as a result of lead exposure Higher IQ losses affected smaller proportions of the population i.e 41/1000 population had losses

of 1.95 IQ points, 10/1000 population had losses of 3.25 IQ points and 5/1000 population had losses of 3.5 IQ points

It was estimated that 1.1 persons per 1000 population were affected by MMR and that 55,000 DALYS were lost as result of lead exposure

Using a similar calculation, the burden of disease in children expressed as the presence

of MMR in the age group 0-4 years, attributable to lead exposure was calculated (Valent et al 2004) Using studies from 11 European Region A countries including one from the UK (O’Donohoe et al 1998), the best estimate blood lead level in children aged 0-4 years was 2.9 µg/dl It was calculated that, 93 children per 1000 population had a loss of 0.65 IQ points as a result of lead exposure Higher IQ losses affected smaller