clinical toxicology in the paediatric patien · clinical toxicology in the paediatric patient ......

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Clinical Toxicology in theClinical Toxicology in the PaediatricPaediatric PatientPatient

Poison Awareness,Poison Awareness,EverybodyEverybody’’s Business.s Business.

Poison Prevention WeekPoison Prevention WeekMay 28 to June 4, 2006May 28 to June 4, 2006

Kingston, JamaicaKingston, Jamaica

DrDr LigiaLigia FruchtengartenFruchtengartenPCC Sao Paulo, BrazilPCC Sao Paulo, Brazil

WHO CEH Training ProjectWHO CEH Training Project

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CHILDREN ARE NOT LITTLE ADULTSCHILDREN ARE NOT LITTLE ADULTS

Until recently, childhoodUntil recently, childhoodenvironmental healthenvironmental healthrisks were consideredrisks were consideredas scaled down risksas scaled down risksfrom adult occupationalfrom adult occupationalrisksrisks

Giotto, National Gallery, Washington DC

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1.1. Different and unique exposuresDifferent and unique exposures

2.2. Dynamic developmentalDynamic developmentalphysiologyphysiology

3.3. Longer life expectancyLonger life expectancy

4.4. Politically powerlessPolitically powerless

Raphael, National Gallery of Art, Washington, DC

CHILDREN ARE NOT LITTLE ADULTSCHILDREN ARE NOT LITTLE ADULTS

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1. DIFFERENT AND UNIQUE EXPOSURES1. DIFFERENT AND UNIQUE EXPOSURES

Unique exposure pathwaysUnique exposure pathwaysTransplacentalTransplacentalBreastfeedingBreastfeeding

Exploratory behaviours leading to exposuresExploratory behaviours leading to exposuresHandHand--toto--mouth, objectmouth, object--toto--mouthmouthNonNon--nutritive ingestionnutritive ingestion

Stature and living zones, microenvironmentsStature and living zones, microenvironmentsLocationLocation –– lower to the groundlower to the groundHigh surface area to volume ratioHigh surface area to volume ratio

Children do not understand dangerChildren do not understand dangerPrePre--ambulatoryambulatoryAdolescenceAdolescence ““high riskhigh risk”” behavioursbehaviours

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1.1. DIFFERENT AND UNIQUE EXPOSURESDIFFERENT AND UNIQUE EXPOSURES

TRANSPLACENTALTRANSPLACENTAL

Lessons from pharmaceuticals:Lessons from pharmaceuticals:thalidomide, diethylstilbestrol (DES), alcoholthalidomide, diethylstilbestrol (DES), alcohol

Many chemicals cross the placentaMany chemicals cross the placentaLead, mercury, polychlorinated biphenyls (PCBs)Lead, mercury, polychlorinated biphenyls (PCBs)……Substances of abuse: alcohol, methadoneSubstances of abuse: alcohol, methadone

Some physical factors may affect the fetus directlySome physical factors may affect the fetus directly Ionizing radiation, heatIonizing radiation, heat

Maternal exposures do matter!Maternal exposures do matter!

EHP

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BREASTFEEDING

Breast milk is the safest and mostcomplete nutrition for infantsMothers should avoid toxic exposuresMilk (human, cow, sheep) can be a marker of

environmental contamination

DDT, DDE, PCBs, TCDD (dioxins),nicotine, lead, methylmercury, alcohol

Morbidity rarely seenUnusual exposure eventMother also ill

WHO

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0

50

100

150

200

250

300

350

400

mg/day

Child (mean)

Child (upperpercentile)Adult

US EPA

BEHAVIOUR AND SOIL CONSUMPTION

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1. DIFFERENT AND UNIQUE EXPOSURES1. DIFFERENT AND UNIQUE EXPOSURESSTATURE AND BREATHING ZONES

Guzelian, ILSI, 1992

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STATURE AND BREATHING ZONES

WHO

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0

0,01

0,02

0,03

0,04

0,05

0,06

0,07

Surface Area/Body Mass

NewbornToddlerChildAdult

SIZE AND SURFACE AREA

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1.1. DIFFERENT AND UNIQUE EXPOSURESDIFFERENT AND UNIQUE EXPOSURES

Pre-ambulatory children are unable to removethemselves from danger

Pre-reading children cannot read warning signs andlabels

Pre-adolescent and adolescent children may takeunreasonable risks because of cognitive immaturity

CHILDREN DO NOT RECOGNIZE DANGER

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2. DYNAMIC DEVELOPMENTAL PHYSIOLOGY2. DYNAMIC DEVELOPMENTAL PHYSIOLOGY

Xenobiotics may be handled differently by an immature body.

Increased energy, water and oxygenconsumption of anabolic state

AbsorptionBiotransformationDistributionEliminationCritical windows of development

WHO

MORE VULNERABLE

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0

100

200

300

400

500

600

<1 4 12 24

liters/kg/day

Age in years

Litr

es

Minute ventilation per kg body weight/day

Miller, Int J Toxicology (2002) 21(5);403

OXYGEN DEMAND

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Maintanence Requirementscal/kg/day ml/kg/day

020

406080

100120140160180

Calories WaterAge in Years

<11.0-3.04.0-6.07.0-10.011.0-1415-1819-2425-5050+

CALORIE AND WATER NEEDS

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A child is building the “body for a lifetime”

The demands of rapid growth and development

Require higher breathing rate, caloric and water intakesSatisfied by enhanced absorption and retention of nutrients

For example:

GI absorption of lead in toddler: 40–70% of oral dose (1/3 retention)GI absorption of lead in non-pregnant adult: 5–20% (1% retention)

ABSORPTION

16Moore, Elsevier Inc, 1973

2. DYNAMIC DEVELOPMENTAL PHYSIOLOGY2. DYNAMIC DEVELOPMENTAL PHYSIOLOGYWINDOWS OF DEVELOPMENT

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Paternal exposure to: Hg, ethylene oxide, rubber chemicals, solvents,linked to spontaneous abortion

Paternal occupation: Painters – anencephaly(Brender, Am J Epidemiol, 1990, 131(3):517)

Mechanics, welders – Wilms tumour(Olshan, Cancer Res. (1990) 50(11):3212)

Textiles – stillbirth, pre-term delivery(Savitz, Am J Epidemiol. (1989) 129(6):1201)

Possible mechanism: impairment of a paternal gene required for the normalgrowth and development of the fetus

“The special and unique vulnerability of children toenvironmental hazards” Bearer, Neurotoxicology, 2000, 21(6):925


WINDOWS OF DEVELOPMENT: FATHERS AND THEIR OFFSPRING

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Pre-conception PCBs and Pb maternal body burdens are linked toabortion, stillbirth and learning disabilitiesFolate deficiency leads to neural tube defects

In utero Thalidomide phocomeliaDES vaginal cancerX-rays leukaemiaHeat neural tube defectsAlcohol FAS (fetal alcohol syndrome)Lead Neurodevelopmental effectsMethyl mercuryPCBs


WINDOWS OF DEVELOPMENT: MOTHERS AND THEIR OFFSPRING

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Vital organ growthBrainLungsKidneysReproductive organs

Physiological functionCentral nervous system Immune systemEndocrine system

Altman eds, FASEB, 1962


WINDOWS OF DEVELOPMENT: BIRTH TO ADOLESCENCE

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3. LONGER LIFE EXPECTANCY3. LONGER LIFE EXPECTANCY

Exposures early in lifeExposures early in lifepermit manifestation ofpermit manifestation ofenvironmental illnesses withenvironmental illnesses withlong latency periodslong latency periods

More diseaseMore diseaseLonger morbidityLonger morbidity

WHO

Children inherit the world WE makeChildren inherit the world WE make

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4. POWERLESS POLITICALLY4. POWERLESS POLITICALLY

No political voiceNo political voice

Advocacy by health sectorAdvocacy by health sector

Environmental laws andEnvironmental laws andregulationsregulationsLocalLocalNationalNationalInternationalInternationalby Ceppi and Corra

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OUTCOME-EFFECTSOrgansSystemsFunctionsDevelopmentSurvival

SUSCEPTIBILITIESCritical windows / timingAgeNutritional statusPoverty

COMPLEX ENVIRONMENTCOMPLEX ENVIRONMENT OFOF CHILDCHILDRENREN ANDANDADOLESCENTADOLESCENTSS

HAZARDSPhysicalChemicalBiological

MEDIAWater - Air - Food - Soil -Objects

SETTINGSRural / urbanHomeSchoolPlaygroundFieldStreetWorkplace

ACTIVITIESLearning, Working, Eating, Drinking, Sleeping, Breathing, Smoking,

Doing sports, Playing, « Testing », Scavenging

Photo credit US NIEHS CERHR logo

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Diagnose and treatDiagnose and treat

Publish, researchPublish, researchSentinel casesSentinel casesCommunityCommunity--based interventionsbased interventions

EducateEducatePatients and familiesPatients and familiesColleagues and studentsColleagues and students

AdvocateAdvocate

Provide good role modelProvide good role model

CRITICAL ROLE OF HEALTH ANDCRITICAL ROLE OF HEALTH ANDENVIRONMENT PROFESSIONALSENVIRONMENT PROFESSIONALS

WHO

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A set of basic and concise questionsA set of basic and concise questions

Part of the standard medical history, with issues:Part of the standard medical history, with issues:

GeneralGeneralSpecificSpecificAgeAge-- and genderand gender--relatedrelated

Tailored according to the localTailored according to the localsituation, needs and capacities of:situation, needs and capacities of:Industrialized countriesIndustrialized countriesDeveloping regionsDeveloping regions

WHAT IS THE PEDIATRIC ENVIRONMENTAL HISTORY?WHAT IS THE PEDIATRIC ENVIRONMENTAL HISTORY?

WHO

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1. What are the potential environmental hazards?What are the potential environmental hazards?

2.2. How, when and where are children exposed?How, when and where are children exposed?

3.3. What are the main effects?What are the main effects?

KEYKEY AREAS TO ADDRESSAREAS TO ADDRESS

WHO

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Set of questions to be prepared locallySet of questions to be prepared locally

Taking into considerationTaking into consideration

1. Potential environmental hazards1. Potential environmental hazards

2. How are children/adolescents exposed?2. How are children/adolescents exposed?

3. Health and developmental effects3. Health and developmental effects

Addressing public health issuesAddressing public health issues

HarmonizedHarmonized -- locally and internationallylocally and internationally

DEVELOPING AND USING THE PEHDEVELOPING AND USING THE PEH

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Symptomatic or asymptomatic childrenSymptomatic or asymptomatic children

Initial basic set of questionsInitial basic set of questions

Detailed questions in special casesDetailed questions in special cases

Clear formulation of specific questions to parents,Clear formulation of specific questions to parents,children, caregivers and teacherschildren, caregivers and teachers

Include home/school/playground auditInclude home/school/playground audit

TheThe ““green pagegreen page”” in a clinical recordin a clinical record

WHEN AND HOW IS THE HISTORY TAKEN?WHEN AND HOW IS THE HISTORY TAKEN?

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WHO

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American Academy of Pediatrics: www.aap.orgATSDR, Agency for Toxic Substances and Disease Registry: www.atsdr.cdc.govChildren's Health and the Environment: www.who.int/ceh

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ENVIRONMENTAL RISK FACTORS AND LONG TERMENVIRONMENTAL RISK FACTORS AND LONG TERMCHILDREN'S STUDIESCHILDREN'S STUDIES

Chemicals

Physical

Biological

Psychosocial

Built environment

Sanitation

Adequate nutritionAdequate nutrition

Media impactMedia impact

Physical activitiesPhysical activities

Social network and participationSocial network and participation

War and conflictWar and conflict

Socioeconomic changesSocioeconomic changes

Life crisesLife crises

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EXAMPLES OF QUESTIONS:EXAMPLES OF QUESTIONS: WHAT ARE THE CHILD'S ACTIVITIES?WHAT ARE THE CHILD'S ACTIVITIES?

HobbiesHobbies

Painting – paint & solvents ?Model-building – glue &solventsPottery – pigments, paints?Gardening – pesticides?Woodwork – chemicals?

ActivitiesActivities

Eating habits (type of diet,food quality).Drinking habits (alcohol useand abuse, soft drinks)Playing habitsLearning habitsWorking habitsScavenging (time spent neargarbage)ExploringTesting (trying drugs, eatingunknown berries)

SportsSports

Type of sportSports areaInjuriesToxic exposuresUse of energizingdrugs

WHOWHO

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EXAMPLES OF QUESTIONS:EXAMPLES OF QUESTIONS: WHAT ARE THE CHILD'S BEHAVIORS?WHAT ARE THE CHILD'S BEHAVIORS?

Personal hygiene and habits

How often does the child bathe?Where? With what?Are the clothes washed regularly?What type of diapers are used?Does the child have lice? How isthe infestation treated?Does the child play on the floor?Carpet?How and how often is the child’sbedroom and play area cleaned?Which chemicals are used to cleanthe home?Does the child have pica?Does the child have hand-to-mouthactivities?

Cultural history

Use of cosmeticsUse of alternative medicinesCultural practicesReligious practicesTraditions involving the useof chemical substances

Transport

What transport does thechild use?- individual or collective;- bicycle;- motorcycle;- horse; or other.

WHO

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We hold our future in our handsWe hold our future in our handsand it is our childrenand it is our children

Poster Contest by HRIDAY with support from WHO SEARO

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With the advice of the Working Group on Training Package for Health CareProviders: Cristina Alonzo MD (Uruguay); Yona Amitai MD MPH (Israel);Stephan Boese-O’Reilly MD (Germany); Irena Buka MD (Canada); LilianCorra MD (Argentina) PhD (USA); Ruth A. Etzel, MD PhD (USA); AmaliaLaborde MD (Uruguay); Ligia Fruchtengarten MD (Brazil); Leda NemerTO (WHO/EURO); R. Romizzi MD (ISDE, Italy); S. Borgo MD (ISDE, Italy)

WHO CEH Training Project Coordination: Jenny Pronczuk MDMedical Consultant: Katherine M. Shea, MD MPH USATechnical Assistance: Marie-Noel Bruné MSc

ACKNOWLEDGEMENTSACKNOWLEDGEMENTS

WHO is grateful to the US EPA Office of ChildrenWHO is grateful to the US EPA Office of Children’’s Health Protection for thes Health Protection for thefinancial support that made this project possible and for the dafinancial support that made this project possible and for the data, graphics and textta, graphics and text

used in preparing these materials for a broad audience.used in preparing these materials for a broad audience.

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DISCLAIMER The designations employed and the presentation of the material in this publication do not imply the expression

of any opinion whatsoever on the part of the World Health Organization concerning the legal status of anycountry, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries.Dotted lines on maps represent approximate border lines for which there may not yet be full agreement.

The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsedor recommended by the World Health Organization in preference to others of a similar nature that are notmentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capitalletters.

The opinions and conclusions expressed do not necessarily represent the official position of the World HealthOrganization.

This publication is being distributed without warranty of any kind, either express or implied. In no event shall theWorld Health Organization be liable for damages, including any general, special, incidental, or consequentialdamages, arising out of the use of this publication

The contents of this training module are based upon references available in the published literature as of June2004. Users are encouraged to search standard medical databases for updates in the science for issues ofparticular interest or sensitivity in their regions and areas of specific concern.

If users of this training module should find it necessary to make any modifications (abridgement, addition ordeletion) to the presentation, the adaptor shall be responsible for all modifications made. The World HealthOrganization disclaims all responsibility for adaptations made by others. All modifications shall be clearlydistinguished from the original WHO material.

clinical toxicology in the paediatric patien · clinical toxicology in the paediatric patient ......

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