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 Cardiff University Heath Park Cardiff CF14 4XN

The views presented in this paper are those of the authors and do not necessarily represent HPA views

July 2005

The burden of disease attributable to environmental pollution

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

1

The burden of disease attributable to environmental pollution 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 2

The burden of disease attributable to environmental pollution

series of distributions, rather than a single reference level such as the nonexposed population. • 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

3

The burden of disease attributable to environmental pollution 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).

4

The burden of disease attributable to environmental pollution 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.

5

The burden of disease attributable to environmental pollution 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.

6

The burden of disease attributable to environmental pollution

Prevalence of treated asthma per 1000 patients For Males (1998)

rate per 1000 LCL UCL No. of Cases

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)

0-4 years

5-15 years

97 93.8 100.2

132.1 129.9 134.3

72.8 70.7 74.8

55.3 53.8 56.8

47.2 45.8 48.5

44.5 43.1 45.9

59.2 57.4 61.1

80.7 78.3 83.2

89.4 85.9 92.9

61.8 55.7 67.9

72.3 71.7 73

73.2 72.5 73.9

3182

11979

4571

5020

4274

3779

3745

3809

2303

373

43035

43035

crude rate (all years)

age standardised rate (all years)

Prevalence of treated asthma per 1000 patients For Females (1998) 0-4 years rate per 1000 LCL UCL No. of Cases

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

62.5 59.8 65.2

104.1 102 106.1

85.2 83 87.5

65.3 63.6 66.9

62.4 60.8 64

64.8 63.1 66.5

79.9 77.8 82

88 85.6 90.4

80 77.4 82.7

52.2 48.7 55.6

76.2 75.6 76.9

76.5 75.8 77.2

1946

9014

5066

5818

5473

5369

4965

4694

3174

829

46348

46348

LCL – Lower Confidence Level; UCL – Upper Confidence Level

7

The burden of disease attributable to environmental pollution 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: Prevalence EAF BODAE Total ▲ rate Population Number of children in England and Wales aged 10-14 years 3425023 29.0% 30% 297977 with wheeze in last 12 months Number of children in England and Wales aged 0-9 years 6401995 29.0% 30% 556974 with wheeze in last 12 months Number of children in England and Wales aged 0-15 years 10488736 12.0% 30% 377594 currently being treated for asthma Number of children in England and Wales aged 0-15 years 10488736 20.5% 30% 645057 with doctor diagnosed asthma Number of adults in England and Wales aged 16 and over 41553180 10.0% 30% 1246595 currently being treated for asthma Number of adults in England and Wales aged 16 and over 41553180 14.5% 30% 1807563 with doctor diagnosed asthma ▲

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

8

The burden of disease attributable to environmental pollution Environmentally attributable prevalence of treated asthma per 1,000 patients in Primary Care Age 0–4 5 – 15 0–4 5 – 15 All ages All ages

Sex

BODAE per 1000 patients 97 x 30% = 132.1 x 30% = 62.5 x 30% = 104.1 x 30% = 72.3 x 30% = 76.2 x 30% =

Male Male Female Female Male Female

29 40 19 31 22 23

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

Mixed asthma

ICD10:J45.8

26 x 30% =

8

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.

9

The burden of disease attributable to environmental pollution

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 fever). Allergic rhinitis affects about 10% of the population, with nasal itching, sneezing, congestion and rhinorrhoea, and it may be accompanied by allergic conjunctivitis (itchy, lacrimating eyes). Mast cell degranulation resulting in inflammation and oedema can be so severe as to block the sinus ostia and Eustachian tubes with resulting secondary bacterial infection. Nasal polyps may occur (mucosal sacs containing inflammatory fluid and cells) and allergen avoidance is difficult. 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:

10

The burden of disease attributable to environmental pollution 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) Skin complaints (Population of children)

52,041,916 x 10% x 30% = 10,488,736 x 11% x 30% =

1,561,257 346,128

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

5.1

Environmental aetiology

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 8090% 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) Disease

ICD10 code

Cases

11

EAF

BODAE

The burden of disease attributable to environmental pollution (no. of cases) Kidney

C64-C66, C68

Brain and CNS

C70-C72

NHL

C82-C85, C96

Leukaemia

C91-C95

All Malignancies (ex. skin)

All C codes (ex. C44)

5.4

males females persons males females persons males females persons males females persons males females persons

33 40 73 173 135 308 54 22 76 202 186 388 660 583 1243

5% 5% 5% 5% 5% 5% 5% 5% 5% 5% 5% 5% 5% 5% 5%

1 2 3 8 6 15 2 1 3 10 9 19 33 29 62

Conclusion

Currently the best available estimate is that between 5% and 90% of childhood cancers may be attributable to toxic chemicals in the environment.

12

The burden of disease attributable to environmental pollution

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).

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The burden of disease attributable to environmental pollution 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. 14

The burden of disease attributable to environmental pollution

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: Disease ADHD

No. of children (0-14)* 9,827,018

Prevalence rate 1.40%

No. of cases** 137578

EAF 10%

BODAE 13757

* 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 as spoken language) • social interaction (reciprocal -includes features like poor eye contact, lack of interest in people) • restrictive, repetitive patterns of behaviour (includes routines and rituals and preoccupations with restricted subjects). Other autistic spectrum disorders, notably Asperger’s syndrome, have similar manifestations to autism but are generally less severe and meet some but not all of the diagnostic criteria for childhood autism. The majority of children with autism (around 2/3) have learning disability (mental retardation) and many develop epilepsy in adolescence. 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

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The burden of disease attributable to environmental pollution 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 Disease

No of children (0-14)*

Autism

No of cases**

Prevalence rate

9,827,018

0.10%

EAF 9827

BODAE 10%

982

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

6C

Learning disability

Definitions The formal definition of ‘learning disabilities’ or ‘intellectual disabilities’ includes the presence of: •

A significant intellectual impairment

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The burden of disease attributable to environmental pollution •

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