pediatric environmental health global situation

Pediatric Environmental Health Global

Situationศ.พญ.สุ�วรรณา เร�องกาญจนเศรษฐ์�

อ.พญ. ร�ชน�วรรณ สุ�น�ทธ์�ก�ลคณะแพทยศาสุตร� โรงพยาบาล

รามาธ์�บดี� มหาว�ทยาล�ยมห�ดีล

Should We Be Concerned?

Data from CDC / National Center for Health Statistics

Increase in Diabetes (1980-2010)

Increase in Autism Prevalence

Increase in ADHD

Increase in Asthma

Should We Be Concerned?

Cancers Birth defects (cleft palate,

cardiac malformations) Reproductive dysfunction

(infertility) Lung dysfunction (asthma,

asbestosis) Neurodegenerative diseases

(Parkinson’s) Neurodevelopmental

disorders (autism) Cardiovascular disease (air

pollution, dioxins) Endocrine disorders (diabetes)

Diseases with a Known or Suspected Environmental Component Include:

“ENVIRONMENT” Includes:

Industrial chemicals

Agricultural chemicals

Physical agents

(heat, radiation)

By-products of combustion and industrial processes (dioxin)

Foods and nutrients

Prescription drugs

Lifestyle choices and substance abuse

Social and economic factors

Climate change and weather effects

Trends in global surface temperature, sea level, and northern hemispheric snow cover over the last 150 years.

(Reproduced from Pachauri RK, Reisinger A, editors: Climate Change 2007 : Synthesis Report)

• พาย�ไซโคลน

• Extreme Heat Event - Heat Stroke - Palm + MI - ใช) A/C => Pollution Asthma + COPD• พ�ช => ขาดีอาหาร => Migration

Climate change and weather effects

• Complete loss or displacement of Succulent Karoo biome projected under climate change, and many species losses in other biomes

• Intensity of extreme events increased significantly over South Africa; biome shifts will favor horticulture over plantation forestry; malaria risk areas projected to expand southward

• Floods in 1999 severely affected coastal population and infrastructure, with long – lasting economic and development impacts; adaptation and recovery very costly and beyond the means of African countries

• East African Great Lakes and reservoirs respond to climate variability with pronounced changes in storage

• Long – lasting impacts of drought on national economics for the Southern African Development Community region

• Coastal marine fisheries likely to be negatively affected by changes in Bangwuela current

Climate Change and Weather Effects1.

Infection2. Ozone depletion 3. Loss of Biodiversity 4. Environmental Endocrine Disruptor (EED)

Infection• Infection & their vector - Mosquito – Breeding นานข+,น - Malaria, Dengue, Encephalitis• Public Health Condition favoring disease

2. Ozone depletion

CFC , UVB => Ocular & Dermatologic effect

=> Immune system• UVB - photoimmunity => Immune

- association – pulm TB เพ�-ม vinalence & rapid - smallpox , Herpes

simplex & papilloma - ร�กษาดี)วย UVB –

psoriasis แล)วดี�ข+,น

Ozone depletion

Infection2. Ozone Depletion3. Loss of Biodiversity

Infection2. Ozone Depletion 3. Loss of Biodiversity • Water

pollution• Air pollution• Soil pollution

Loss of biodiversityWater Pollution Fecal contamination -> waterborne gastroenteritis

Cholera, Dysscentery, Typhoid, Trachoma

Virus - gastroenteritis - HAV - Polio

Parasite - Protozoa - Helminths -

Schislosome - Others - Sarcoptes scabie, Ringworm Natural Toxin - Arsenicosis

- Fluorosis - Lead - Organic ; Benzene

, Toluene - Inorganic ;

Arsenic , Copper

Air Pollution• PM 10 : penetrate เข)าปอดี• So2 and No2

• Ground Ozone - No2 or VOC => inflammation of lung tissue

exacerbate asthma & chronic lung - ผิ�วหน�ง => itching & swelling systemic => immune system• Allergens – asthma

Soil Pollution• Pesticides - Acute Organochlorine – Persistent Organic Pollutant (POPs) Organophosphate poisoning

- Chronic birth defect (cleft palate, musculoskeletal, CNS), neuro problem ( Memory & Parkinson), skin, DM and CA (non – Hodgkin lymphoma, leukemia, sarcoma, prostate CA, MM) infertility - Sewage & Rotting organic materials

DDT (Dichlorodiphenyl trichloroethane) เป0น EED - affect developmental and reproductive health

- genetic disruption risk to cancer & DM

Soil Pollution

Infection2. Ozone depletion 3. Loss of Biodiversity 4. Environmental Endocrine Disruptor (EED)

Environmental Endocrine Disruptor (EED)

Chemicals that in vitro possess an

ability to act on

the endocrinologic system (children are

susceptible than adults) eg. herbicides,

fungicides,

plasticizers

EED great concern in children

Bisphenol A : weak estrogen found in many

plastics

Phthalates : an agent commonly used in

plastics with suspected spermatotoxic effects

PCB : can affect the duration of lactation and

menache

Arsenic – toxic to adrenal cortex

Perchlorates

Dioxin

Toxic to thyroid

Pediatric environmental health is a relatively new discipline that examines the effects of environmental agents on the health of children.

Children have greater risk of exposure to environmental agents, as well as greater susceptibility to toxic effects, than adults.

A number of environmental pollutants are more likely to produce clinical toxicity in children than in adults. These include lead, mercury and polychlorinated biphenyls.

Overview of Children’s development features that can affect

Toxicokinetics

Environmental Toxins relevant to children’s healthAir particulates Mercury

Arsenic Ozone

Asbestos Perchlorates

Carbon monoxide Pesticides

Environmental tobacco smoke (ETS)

Polybrominated dipheyl ethers (PDBE)

Indoor air pollutants

Polybrominated biphenyls (PCBs)

Lead Radon

M-tert-butyl ether (MTBE)

TrichloroethyleneHaddad and Winchester’s Clinical Management of Poisoning and Drug overdose, 2007

The dose-response curve of potential toxins, including drugs, chemicals, and physical agents, can have threshold deterministic and stochastic effects

Redrawn from WHO World Health Report, 2002.©WHO 2005

Deaths from indoor smoke from Solid fuels

Photo courtesy of Dr. Molly Kile , Harvard School of Public health

Hyperkeratotic rash of arsenic intoxication

Photo courtesy of Dr. Molly Kile , Harvard School of Public health

Hyperkeratotic rash of arsenic intoxication

Pediatric Considerations - Lead

Children absorb lead more

efficiently than adults

Children who are malnourished

are particularly susceptible to

lead due to lower intakes of

iron and calcium which can

reduce the absorption of lead

Blood lead levels > 10 g /dL

among children are considered

elevated, but no level is

considered safe

Health Effects Associated with Fibrogenic and Metal Dusts

Asbestos Silica Cotton Dust Coal Dust

Metals Lead Manganese Chromium Beryllium Mercury

(inorganic)

Health Effects Associated with Fibrogenic and Metal Dusts

Adverse Health Effects Caused by Selected Classes of Pesticide*

Insecticide Borates Carbamates Organochlorines Organophosphates

Insecticide

Rodenticide Coumarins Fluoroacetate Metal phosphides Strychnine Thallium

Rodenticide

Herbicides Dipyridil Phosphonates Triazines

Herbicides

Fungicide Mercury, organic Halocarbons (fumigant)

Organotin Phenol derivatives (fungicide, wood preservative)

Fungicide

Others Arsenicals Chloralose Diethyltoluamide (insect repellent)

Others

Pediatric Consideration -

Pesticides Approximately 70% of working children work in agriculture and may be exposed to pesticides at occupational levels worldwide.

Children are particularly vulnerable to the effects of pesticides because they have lower levels of enzymes involved in the metabolism and excretion of pesticides such as organophosphates.

Pediatric Consideration

Children may be more likely to be exposed to some contaminants and toxins due to hand-to-mouth activity

For a given exposure, children have greater exposures per unit of body weight

Children less efficiently metabolize and excrete many toxic chemicals

Mold / Food Impurities Aflatoxin Ergotism Farmer’s lung disease Melamine

Outlines What is environmental pediatric?

Hazards specific to children

Toxic effects of selected manufactured chemicals

Air quality Anticipatory guidance

“Health and disease in children and that diagnoses, treats, and prevents diseases

and disabilities caused in children by environmental

exposures.”

What is environmental

pediatrics?

Landrigan PJ, Miodovnik A.Mt Sinai J Med. 2011 Jan-Feb;78(1):1-10.

Many Endpoints / Outcomes Cancer and birth defects are

not the only endpoints Complex diseases have

complex causes Obesity, diabetes,

cardiopulmonarydisease, cancer, autoimmune disease, neurodevelopmental disorders, schizophrenia,addition, depression are some diseases where the environment acts through epigenetic mechanisms.

OLD… chemicals act by overwhelming the body’s defenses by brute force at very high dosesNEW… chemicals can act like hormones and drugs to disrupt the control of development and function at very low doses to which the average person is exposedNEW… susceptibility to disease persists long after exposure (epigenetics)

Conceptual Shift for Environmental Health Sciences

Windows of Susceptibility

Development is sensitive time for exposureoRapid GrowthoActive and extensive cell

differentiation oIncreased metabolic rateoDeveloping immune system oOpportunities for initiation of

lesions and promotion of altered cells

oDevelopment is a highly integrated process

oProgramming (epigenetic marks set)

Adolescence also sensitive time for development

Greater exposures than adults to toxic chemicals on a body-weight basis

Metabolic pathways are immature

Incredibly rapid, but exquisitely delicate developmental processes are easily disrupted

More time than adults to develop chronic diseases that may be triggered by harmful exposures in the environment

Behavior and development

Adolescence also sensitive time for development

Landrigan PJ, Miodovnik A.Mt Sinai J Med. 2011 Jan-Feb;78(1):1-10.

Windows of Susceptibility

Early Prenatal Mid-Late

Prenatal Postnatal

Week 1-16 Week 17-

40 Birth –25

Central nervous system (3wks - 20 years)

Ear (4-20 wks)

Kidneys (4-40 wks)Heart (3-8)

Immune system (8-40 wks; competence & memory birth-10yrs)

Limbs (4-

Lungs (3-40 wks; alveoli birth-10yrs)Reproductive system (7-40wks; maturation in

puberty)

Skeleton (1-12 wks)

Source: Altshuler, K; Berg, M et al. Critical Periods in Development, OCHP Paper Series on Children's Health and the Environment, February 2003.

Gestation Childhood Reproductive Life Middle Life Later LifePuberty

Environmental Exposures

Developmental Origins of Disease:

Developmental Stressors Lead to Disease Throughout

AGE 2 12 25 40 60 70

Learning Differences/Behavior

AsthmaIncreased Sensitivity

to InfectionsTesticular Dysgenesis

Syndrome

Obesity

Altered Puberty

Infertility

FibroidsPremature Menopause

Breast Cancer

AtherosclerosisCardiovascular

Disease

Prostate Cancer

Alzheimer's

Parkinson's

Examples of Developmental Origins ofHealth and Disease (DOHAD)

The study of changes in DNA expression that are independent of the DNA sequence.

A person’s DNA base sequence doesn’t change, but expression of DNA is affected by changes in DNA “packaging.”

Environment is critical factor in DNA expression; we’re born with genes, but environment affects epigenetic changes.

Epigenetics

DISEASE

EPIGENOME

Adverse health outcomes

CancerCardiopulmonary

diseaseAutoimmune disease

ObesityDiabetes

Neurodevelopmental disorders

SchizophreniaAddiction

Depression

Epigenetic Changes Have Been Implicated in

a Wide Variety of Human Diseases

Normal processesDevelopment

Cell differentiation Aging

GENOME

External influencesEnvironmental

exposures Nutrition

Chemical toxins Metals

Mediators of stress Drugs of abuse

Infection (including HIV)

Effects of selected chemical pollutants on infants and

childrenCHEMICAL

POLLUTANTEFFECT(S)

DiethylstilbestrolAdenocarcinoma of the vagina after intrauterine exposure

ThalidomidePhocomelia after intrauterine exposure

TrichloroethyleneElevated risk of leukemia after intrauterine exposure

AlcoholFetal alcohol syndrome after intrauterine exposure

LeadNeurobehavioral toxicity from low-dose exposure

Nitrosamine, vinyl chloride, ionizing radiation

Increased risk of cancer after intrauterine exposure

Organophosphate insecticides

Developmental neurotoxicity

Nelson, Ed 19th

Lead Child labor Pesticides Persistent organic pollutants (POPs)

Fluoride Endocrine disruptors: POPs, arsenic

Guidotti TL, Gitterman BA. Pediatr Clin North Am. 2007 Apr;54(2):335-50

Prenatal exposure to organophosphate (OP) pesticides can lower a

child’s IQ

Pesticides Herbicides, insecticides,

fungicides, rodenticides Used to prevent, destroy, repel,

or mitigate pests (insects, microbe, animals) or unwanted plants

Found in air, soil and water

Pesticides

Recent NIEHS Studies on Pesticide Effects

• High Pesticide Exposure Events (HPEE) & Cognitive Decline

- One or more HPEE may contribute to adverse CNS outcomes independent of diagnosed pesticide poisoning.

- Findings part of Agricultural Health Study.

• Two Pesticides Associated with Parkinson’s Disease

- People who used either rotenone or paraquat developed Parkinson's disease approximately 2.5 times more often than non-users.

Persistent organic pollutants (POPs)

Halogenated, carbon-based chemicals

Resist the natural mechanisms of catabolism in the environment

Organochorine pesticides: toxaphene, chlordane, DDT, mirex, aldrin, dieldrin

Polychlorinated biphenyls Chlorinated dibenzo-dioxins Furans

Halogenated carbon-based chemicals Unchanged for long periods Organochlorine pesticides:

toxaphene, chlordane, DDT (dichloro-diphenyl-trichloroethane), mirex, aldrin, and dieldrin

Polychlorinated biphenyls, chlorinated dibenzo-dioxins and furans

Lipophilic: liver and adipose tissue, and organisms with extensive body fat (seals)

Migrate within the ecosystem

Effect Dioxin-like

metabolic effects, cancer risk, and endocrine-mimic activity

Immune defect

Environmental Chemicals in the Development of

Diabetes and Obesity Exposure to certain chemicals

or chemical classes has been associated with the development of diabetes or obesity in humansArsenic Persistent organic

pollutants (POPs)Bisphenol A (BPA)

Pesticides

Trialkyltins (“Organotins”)

Phthalates

Maternal Smoking

Nicotine

Fluoride

• Flurosis: Dental, skeletal

• Fluride overexposure: Africa, Middle east, India, Mexico, China, Bangaladesh

Endocrine disruptors

Exogenous chemicals that mimic or modify the action of endogenous

hormones and alter the normal functioning of the endocrine system

Endocrine disruptors

Potential adverse outcomes: neurodevelopmental, neurobehavioral, reproductive, immune related, or cancer related

Route of exposure: ingestion, transplacenta

Increasing incidence of testicular cancer, hypospadias, early onset of puberty in girls

POPs and others Low level chronic

exposures???, timing of exposure

Arsenic

Acute poisoning: Bangladesh, India Cancer, skin disease, neurotoxicity,

malnutrition (wasting effect)

Arsenic

Arsenic Risk factor, along with lead, mercury,

and deficiency in omega-3 fatty acid intake reduces IQ and academic performance

Need for Chemical Testing

Over 80,000 chemicals in commerce today Majority of chemicals in commerce are untested 100 chemicals: impair brain development in

animal models 12 chemicals (alcohol, lead, mercury, etc.):

closely associated with human cognitive impairment

An evidence-based review of known toxic effects of selected

manufactured chemicalsChemical What is it? Where is it

found and how does exposureoccur?

Evidence-based health effects

Benzene Precursor for other chemical compounds

Air, water, soil: • outdoor air: tobacco smoke, gas stations, motor vehicle exhaust, industrial emissions • vapors from certainproducts (glues, paints, furniture wax, and detergents)•plastics, resins, nylon, synthetic fibers, rubbers, lubricants, dyes, detergents, drugs, pesticides

Carcinogenic, dizziness, tachycardia, headaches, tremors, and confusion, vomiting, gastritis, sleepiness, seizures, death, irregular menses, decrease in ovarian size

manufactured chemicalsChemical

What is it? Where is it found and how does exposureoccur?

BPA (Bisphenol A)

used to make polycarbonateplastics and epoxy resin lining of aluminum cans

•plastic #7 products and in the plastic additive inside of aluminum cans•toys, drink containers, medical equipment (intravenous tubing), dentalsealants, liquid infant formula, canned foods, and thermal paper (paper that has been heated, such as receipts)

Associated with cardiovasculardiagnoses, type 2 diabetes, and elevatedliver enzymes; injury to placental cellsexposed to BPA

Dioxins A group of chemicals that are byproducts ofchlorination (bleaching) processes atindustrial sites and waste and watertreatment plants

air, water, and soil; these chemicals can build up in the food chain; consumptionof contaminated food (meat, diary, and fish)consists of most of the populationsexposure to this group of chemicals

carcinogenic; it also may cause dermatologic effects (chloracne,discoloration, and hirsutism), elevation ofliver enzymes, glucose metabolismalterations, and subtle hormonal changes

Chemical What is it? Where is it found and how does exposureoccur?

Formaldehyde

Water-soluble gas most frequently used asa precursor to other chemical compounds

•wood products, plastics, paints, human-made fibers, fertilizer, resins, preservative in household products, or cosmetics•smog, cigarettes,gas cookers, fireplaces, medical supplies,manufactured wood products, fiberglass, carpets, permanent press fabrics, paper products,and household cleaners

•Carcinogenic•Irritation of eyes,nose, throat and skin•Exacerbates asthma

Melamine •Metabolite of a pesticide (cryomazine) •Decomposition product of a food equipment sanitizer (trichloromelamine)

•food products produced in China•plastic tableware,flame retardants, paper/paperboard, andindustrial coatings

Crystalluria irritation anywhere along the urinary tract,nephrolithiasis, or acute renal failure

manufactured chemicals

Chemical What is it? Where is it found and how does exposure occur?

PBDEs(polybrominated diphenyl ethers)

•Flame-retardant chemicals added to plastics and foam products•Chemically related to PCBs and are considered POPs

Air, water, soil, and dust:manufacturing and use of consumer products •foam pillows, carpet padding, furniture, airplane seats, textiles, baby care items, and plastic casings of computers, cell phones, TV, and remote controls

•Learning and memory•Deficits motor changes and reactivity to the environment•Decreased thyroid level•Possible carcinogen

PCBs(polychlorinated biphenyls)

manufactured of PCBs was stopped in 1977 (toxic effects)persist for decades in theenvironment and were found in UCB of a random sample of newborns as late as 2005

•Manufactured before 1977 (fluorescent lighting fixtures, electrical devices)•Contaminated food, mainly fish, meat, anddairy products•Air near hazardouswaste sites •contaminated wellwater

•Suspected carcinogen•Preterm birth•Tooth abnormalities•Rashes •Liver damage•Motor delay and decrease in short-term memory

Chemical What is it? Where is it found and how does exposureoccur?

PFOAs(perfluorooctanoic acids)

Manufactured chemical that repels oil, grease, or water

•surface protection products (carpet and clothing treatments)•Coating for paper and cardboard packaging andfire-fighting foams•air, soil, food, water carried over greatdistances by groundwater or ocean currents

•At high doses, fetal weight reduction,cleft palate, delayed bone ossification,stunted mammary gland development,immunotoxicity, thyroid hormone disruption, cardiac abnormalities, and/or death

Phthalates Use in soft, flexible plastics, PVC and personal care products

•Air, water, food•Exposure: ingestion, inhalation, topical •Food packaging, medical tubing, wire insulation,construction products, and toys

•Androgenization(feminizaion) with prenatal exposure•Rhinitis, eczema, asthma in early childhood exposure

Used to make polycarbonate plastics and epoxy resin lining of aluminum cans

Found in plastic #7 products and in the plastic additive inside of aluminum cans, toys, drink containers, medical equipment (e.g., intravenous tubing), dental sealants, liquid infant formula, canned foods, and thermal paper

Cardiovascular disease, type 2 DM, and elevated liver enzymes

BPA (Bisphenol A)

Bevacqua J.J Pediatr Health Care. 2013 Jan;27(1):13-22.

Metabolite of a pesticide (cryomazine), decomposition product of a food equipment sanitizer (trichloromelamine)

2008: food products produced in China (e.g., infant formula, foods with milk-derived ingredients, eggs, pet food);

Plastic tableware,flame retardants, paper/paperboard, and industrial coatings

Crystalluria irritation anywhere along the urinary tract, nephrolithiasis, or acute renal failure

Melamine

Phthalates Manufactured

chemicals used in soft, flexible plastics, PVC, and personal care products

Air, water, and food Pediatric exposure

largely occurs through ingestion, sucking/mouthing plastics, dust inhalation, topical exposure;

Food packaging, medical tubing, wire insulation, construction products, and toys may contain phthalates

Androgenization (feminization) with prenatal exposure

Breast milk exposure: sex hormone disruption and human binding globulin disruption in male infants;

Early childhood exposure: rhinitis, eczema, and asthma

Air quality

Air pollution: 3 types Ambient air pollution: CO, PM Air toxics Indoor air pollution

Health effects of the air pollution

Neurodevelopment

Asthma: NO, O3, PM2.5

Immune effects: viral infection

Reproductive Lung capacity:

NO, PM2.5 Atopy? ETS: asthma,

pneumonia, middle ear infection, SIDS

Asthma host defenses and immune

effects reproductive outcomes The early development of lung

capacity Asthma is triggered by several

air pollutants individually and in combination, including oxides of nitrogen, ozone, and fine particulate matter

Ambient air pollution

Indoor air pollution

• Acute lower respiratory tract infections,

• Severe infant morbidity and mortality

• Environmental tobacco smoke: increased incidence of asthma, pneumonia, and middle ear effusion

Precursor for other chemical compounds Found in air, water, and soil

outdoor air: tobacco smoke, gas stations, motor vehicle exhaust, and industrial emissions

vapors from certain products (e.g., glues, paints, furniture wax, and detergents)

plastics, resins, nylon, synthetic fibers,rubbers, lubricants, dyes, detergents,drugs, and pesticides

Carcinogenic Drowsiness, dizziness, tachycardia,headaches, tremors, and

confusion, vomiting, gastritis, sleepiness, seizures, tachycardia, or death

Irregular menses and decrease in ovarian size

Benzene

When giving anticipatory guidance, should

recognize that although no one can do everything,

everyone can do something.

Anticipatory guidance

Avoid pesticides Use non-toxic products Clean up indoor air Eat healthy Be wise with plastics

Anticipatory guidance for patients and families

Agency for Toxic Substances and Disease Registry: http://www.atsdr.cdc.gov

Centers for Disease Control & Prevention: http://www.cdc.gov/environmental/

EnviRN Knowledge Network, Nursing and Environmental Health: http://envirn.org

Pediatric Environmental Health Specialty Units: http://www.aoec.org/pehsu.htm

World Health Organization: http://www.who.int/ceh/en/

Resources

pediatric environmental health global situation

climate change

climate variability

infection infection

weather effects trends

pollution asthma copd

air pollution pm

complete loss

health statistics

Education

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