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Association of Earlylife Exposure to Household Gas Appliances and Indoor Nitrogen Dioxide With Cogni

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Half the world's population is exposed ... Exposure assessment ... Role of maternal genotypes in modifying the adverse effects of early-life exposures? ... – PowerPoint PPT presentation

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Title: Association of Earlylife Exposure to Household Gas Appliances and Indoor Nitrogen Dioxide With Cogni


1
  • Association of Early-life Exposure to Household
    Gas Appliances and Indoor Nitrogen Dioxide With
    Cognition and Attention Behavior in Preschoolers
  • Jordi Sunyer, M.D.
  • Centre for Research in Environmental Epidemiology
    (CREAL), Barcelona, Spain
  • jsunyer_at_creal.cat
  • Website www.creal.cat

2
Deleterious effects of air pollution on
childrens neurodevelopment (1) polycyclic
aromatic hydrocarbons
Source Perera et al. Environ Health Perspect.
2006114(8)12871292.
3
Deleterious effects of air pollution on
childrens neurodevelopment (2) black carbon
particles
Source Suglia et al. Am J Epidemiol.
2008167(3)280286.
4
Importance of indoor air pollution
  • Although outdoor air pollution first brought the
    issue of the health effects of air pollution to
    the publics attention
  • It likely has the greatest impact on childrens
    health and constitutes a public health problem in
    both developed and developing countries
  • Half the worlds population is exposed
  • Globally, it is estimated to cause 36 of all
    lower respiratory infections and 22 of chronic
    obstructive pulmonary disease

5
Major sources of indoor air pollution
  • Combustion by-products from heating and cooking
  • High prevalence of gas stoves in developed
    countries (5070),
  • High indoor levels of nitrogen dioxide can be
    produced, the most toxic of oxides of nitrogen
    and the most extensively studied indoor pollutant

6
Glutathione S-transferase family
  • Polymorphic (allelic variants) GSTP1, GSTT1,
    GSTM1 and GSTM3
  • Antioxidant activity (oxidative stress) ROS,
    lipid peroxidation, inflammatory process
  • GSTP1 is the most strongly expressed isoenzyme in
    the human brain during early life
  • Cell damage induced by NO2 is mediated by oxidant
    injury, inflammatory response and lipid
    peroxidation
  • We hypothesize that detoxification genes may
    modify the neurologic effect of nitrogen dioxide.

7
Objectives
  • To investigate the effect of early-life exposure
    to household gas appliances and indoor nitrogen
    dioxide on cognitive functioning and inattention
    hyperactivity symptoms in preschoolers.
  • We also assessed whether these effects differ by
    polymorphisms of GSTP1.

8
Methods Study population and design
  • A population-based birth cohort was recruited on
    the island of Menorca (Spain)
  • Recruited were all women presenting for prenatal
    care in Menorca over 12 months starting in
    mid-1997.
  • 482 children (94 of those eligible) were
    enrolled, and complete outcome data were provided
    for 422 (87) up to 4 years of age.
  • 411 children (85) were genotyped.
  • The present paper is based on 398 children with
    complete information on neurodevelopmental
    assessment, gas appliances at home, and indoor
    nitrogen dioxide concentrations

9
Assessment of the outcomes of interest
  • Neurocognitive functions and motor skills were
    measured with the Spanish version of the McCarthy
    Scales of Childrens Abilities test, consisting
    of 6 different scales (general cognitive, verbal,
    perceptual-performance, quantitative, memory, and
    motor)
  • ADHD was evaluated by using Diagnostic and
    Statistical Manual of Mental Disorders, 4th
    Edition, criteria

10
Exposure assessment
  • Questionnaire on household characteristics
    (cooking appliances, heating and cooling systems,
    number of hours of ventilation, and size of the
    house)
  • Average 2-week nitrogen dioxide concentrations
    were measured by passive diffusion tubes
    installed in the living room wall at a height of
    2 m and away from any window or air conditioner

11
Genotyping methods
  • DNA was extracted from blood (87) and saliva
    (13) samples.
  • Two semiautomated assays were implemented to
    facilitate detection of the coding variant
    Ile105Val in GSTP1 that variant was analyzed by
    using pyrosequencing technology (Biotage,
    Uppsala, Sweden) in a single assay.
  • All assays were performed by technicians blinded
    to neurodevelopmental outcomes and exposure
    information.
  • GSTP1 genotypes were in Hardy-Weinberg
    equilibrium in the total analyzed cohort (P gt
    0.05).

12
Statistical analysis
  • Prediction of indoor NO2 using a regression
    model, regressing the 2-week average values of
    nitrogen dioxide against type of stove (electric,
    gas), gas fire (no, yes), use of extractor fan
    when cooking (always, sometimes, never), number
    of gas appliances at home, and season (winter,
    spring, summer, autumn)
  • Stratified the analysis according to GSTP1
    genotypes.
  • We used multivariate linear and logistic
    regression models

13
Comparison of the Distribution of Child
Variables Between Preschoolers Included and Not
Included in the Menorca Cohort, Spain, 19971999
14
Comparison of the Distribution of Maternal
Variables Between Preschoolers Included and Not
Included in the Menorca Cohort, Spain, 19971999
15
Comparison of the Distribution of Exposure
Variables Between Preschoolers Included and Not
Included in the Menorca Cohort, Spain, 19971999
16
Determinants of Indoor NO2 Concentration (ppb),
Menorca Cohort, Spain 1997-1999
17
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18
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19
Adjusted general additive models
Relation (and 95 confidence interval) between
predicted indoor nitrogen dioxide (NO2)
concentration and cognitive function scores
adjusted for maternal social class, maternal
education, school trimester at testing, evaluator
(neuropsychologist), maternal smoking during
pregnancy, number of smokers at home, maternal
consumption of alcohol during pregnancy, and home
location. Menorca cohort, Spain, 19971999. The
symbols on the x-axes indicate NO2 observations.
20
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21
Findings replication in Sabadell cohort
22
Bayley mental and psychomotor development index
at 14 months of age in relation to gas cooking
during pregnancy. Sabadell cohort, Spain,
2004-2006 (N557)
a Reference category is no gas cooker b Model 1
sex, age (centered, in days), psychologist c
Model 2 sex, age (centered in days),
psychologist, maternal social class, maternal
education, maternal IQ d Model 3 sex, age
(centered in days), psychologist, maternal social
class, maternal education, maternal IQ, maternal
age, maternal country of origin, age of the house
Source Vrijheid et al. Exposure to gas cooking
and neurodevelopment in the first years of life
(unpublished data).
23
Bayley mental and psychomotor development index
at 1 to 1½ years of age in relation to gas
cooking during pregnancy, by GSTP1 Ile105Val
genotype of the child. Only children with Spanish
and white parents (N356)
a Regression coefficient for the effect of gas
cooking. Reference category is no gas cooker. b
Model 1 sex, age (centered, in days),
psychologist c Model 2 sex, age (centered in
days), psychologist, maternal social class,
maternal education, maternal IQ d Model 3 sex,
age (centered in days), psychologist, maternal
social class, maternal education, maternal IQ,
maternal age, age of the house
Source Vrijheid et al. Exposure to gas cooking
and neurodevelopment in the first years of life
(unpublished data).
24
Limitations
  • Small numbers of subjects in each subgroup limit
    the conclusions about gen-environment
    interactions in a single study
  • Potential effect of unmeasured indoor air
    contaminants?
  • Contribution of outdoor nitrogen dioxide to
    indoor nitrogen dioxide levels?
  • Conclusions could not be extended to further time
    periods of exposure, although we expect the
    larger effect during early life
  • Role of maternal genotypes in modifying the
    adverse effects of early-life exposures?

25
Main remarks
  • Gas stove is largely used in developed countries
  • Ventilation should be recomended as a general
    practice
  • Avoid to have children in the kitchen while
    cooking

26
Next steps
  • Increase statistical power Analysis data from
    all cohorts of the INMA project
  • Differentiating type of gas fuel (gas natural,
    propane, butane).

27
Acknowledgments
  • Eva Morales
  • Martine Vrijheid
  • Maties Torrent
  • Raquel Garcia-Esteban
  • Monica Guxens
  • Jordi Julvez, Joan Forns, Muriel Ferrer
  • The field workers and participants.
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