Montreal Lead Study: Association between
Cumulative Lead exposure index and Blood lead levels in
1-5 Years-old ChildrenGerard Ngueta, (PhD Candidate in Epidemiology)
Research Advisor: Dr. Patrick Levallois
GG
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Montreal Lead Study
Undertaken in 2009 and firstly designed to assess lead exposure in 1-5 years old children living in Montreal city
US E.P.A reports indicating the global decrease of environmental lead exposure and huge reduction of BLL in young children.
Montreal Study remains relevant because of poor data published in Canadian children (aged under 6).
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Strong association between environmental lead and BLL
Reported in several previous studies and reports
In most cases, they were cross-sectional association studies
Most of children included were those with high risk of lead exposure [Black and Hispanic origin > 50% population study]
The present study differs from earlier: 1) Caucasian children ≈ 67% of population study2) Cumulative lead exposure index (CLEI) in addition to cross-
sectional measures of exposure
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Motivation for using CLEI ? Previous studies indicated that lead has a half-life of approximately
30 days in the blood
Greenbalt reported that the time required to find steady-state is approximately four-to-five times the elimination half-life after a single exposure [Annual review of medicine 36, 421-427]
There is a scientific reason to believe that BLL at a given time is more related to lead exposure experienced during 3-5 months before that time.
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Motivation for using CLEI ?
Days Environmental lead Blood lead
149 X149
148 X148
…. ….
3 X3
2 X2
1 X1
Day of visit X0 Y
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Motivation for using CLEI ?
Days Environmental lead Blood lead
149 X149
148 X148
…. ….
3 X3
2 X2
1 X1
Day of visit X0 Y
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Motivation for using CLEI ? Previous studies indicated that lead has a half-life of approximately
30 days in the blood
Greenbalt reported that the time required to find steady-state is approximately four-to-five times the elimination half-life after a single exposure [Annual review of medicine 36, 421-427]
There is a scientific reason to believe that PbS at a given time is more related to lead exposure experienced during 3-5 months before that time.We hypothesize that cumulative lead exposure would be more suitable to assess the association between Environmental lead and BLL
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Objectives of study To estimate the effects of both CLEI and cross-sectional measures of
water lead and residential dust lead on BLL in children aged 1 to 5.
To assess the association between both measures of exposure and the likelihood of BLL greater or equal to 2 µg/dl.
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Where are children from ? Selected from four large districts:
1) Mercier-Hochelaga-Maisonneuve2) Saint-Laurent3) Verdun4) Villeray-Saint-Michel-Parc-Extension
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Who are they?
306 children aged under 6
Child should drink tap water regularly [1]be born in Canada, [2]live in the residence for at least one year, [3]not live outside home more than 2 days per week [4] no suffer from severe disease [5]
Families should not use a water filtration system [6]Families should live in single-house unit or multi-units apartments with 3 levels or less [7]
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Who are they?
Age (Months)
12-23 50 (16%)
24-35 66 (22%)
36-71 190 (62%)
Girls 153 (50%)
Caucasians 207 (68%)
Day Care attendance 229 (75%)
Mother with university degree
221 (73%)
Hand-to-Mouth behaviour 148 (49%)
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Who are they?
Age (Months)
N (%) BLL † BLL ≥ 2 µg/dL
12-23 50 (16.0%) 1.27 (0.91 – 1.76)
7 (14.3%)
24-35 66 (22.0%) 1.40 (1.00 – 1.91)
16 (24.6%)
36-71 190 (62.0%) 1.31 (0.95 – 1.72)
30 (16.3%)
Median (p25-p75): Expressed in µg/dL
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Samples collection
Largely described elsewhere
Water samples
WLLF5 WLLS1
WLLS2
WLLS3
WLLS45 min
flushing30 min of
stagnation
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Sample collection
Largely described elsewhere
Water samples
Dust samplesWindowsill dust : Floor dust: sampled in the center of the available floor space 1) Child’s room 2) Home entrance 3) Another room frequently used
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Sample collection
Largely described elsewhere
Water samples
Dust samples
Paint samples
1) X-ray fluorescence evaluation2) Collection of paint chips and lab measurement of lead level
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Cumulative lead exposure index
Firstly: Modeling seasonal changes of environmental lead
CLEI for water
CLEI = Qe*0.50*∑ [WLLi*exp(-(Ln 2/30)*(N-i))] (expressed in µg)
Daily amount of water consumed
mean water lead level observed for the day i before
day of visit
Gastrointestinal absorption rate
N from 0 to 149
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Cumulative lead exposure index
Firstly: Modeling seasonal changes of environmental lead
CLEI for water
CLEI = Qe*0.50*∑ [WLLi*exp(-(Ln 2/30)*(N-i))] (expressed in µg)
Worst-case exposure scenario: refers to the highest water lead concentration in the samples collected after stagnation time of 30 minutes. Best-case exposure scenario: refers to the sample collected after 5 minutes of flushing
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Cumulative lead exposure index
Firstly: Modeling seasonal changes of environmental lead
CLEI for water
CLEI = Qe*0.50*∑ [WLLi*exp(-(Ln 2/30)*(N-i))] (expressed in µg)
CLEI for dust
CLEI = Qe*0.30*DLL*∑ [exp(-(Ln 2/30)*(N-i))] (expressed in µg)
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Statistical analysis
Linear regression Ordinary least square evaluation Effect estimates Standardized partial regression coefficients Independent contribution of each exposure
To estimate the effects of both CLEI and cross-sectional measures of water lead and residential dust lead on BLL in children aged 1 to 5.
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Statistical analysis
Logistic regression Maximum-likelihood estimation Effect estimates
To assess the association between both measures of exposure and the likelihood of BLL greater or equal to 2 µg/dl.
Crude models
Semi-adjusted models
Adjusted models
Each exposure variable alone
Models including all exposure variables
Full model including all covariates
Propensity Score methods
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Unadjusted linear effectsAdjusted CLEI effectsAdjusted Cross-sectional effectsLikelihood of BLL ≥ 2 µg/dL
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Unadjusted linear effects of environmental lead on BLL
Cumulative lead exposure index † Cross-sectional measure of exposure ††
Estimate 95% CI R-Square Estimate 95%CI R-Square
Intercept 0.1459 0.0714; 0.22050.0986
Intercept 0.2116 0.1393; 0.28380.0353
Water (Worst scenario) 0.0665 0.0431; 0.0899 Water (Worst scenario) 0.0170 0.0067; 0.0274
Intercept 0.1587 0.0866; 0.23080.0964
Intercept 0.1786 0.1050; 0.25210.0667
Water (Best scenario) 0.1231 0.0792; 0.1670 Water (Best scenario) 0.0591 0.0338; 0.0844
Intercept 0.2318 0.1650; 0.2987 0.0501 Intercept 0.2295 0.1613; 0.2977
0.0465Windowsill dust loading 0.0003 0.0001; 0.0004 Windowsill dust loading
0.0033 0.0015; 0.0051
Intercept 0.2412 0.1761; 0.30640.0294
Intercept 0.2440 0.1793; 0.30880.0277
Floor dust loading 0.0022 0.0007; 0.0036 Floor dust loading 0.0243 0.0078; 0.0408
1) R-Squares obtained with CLEI were greater than those by modeling cross-sectional exposure.
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Unadjusted linear effects of environmental lead on BLL
Cumulative lead exposure index † Cross-sectional measure of exposure ††
Estimate 95% CI R-Square Estimate 95%CI R-Square
Intercept 0.1459 0.0714; 0.22050.0986
Intercept 0.2116 0.1393; 0.28380.0353
Water (Worst scenario) 0.0665 0.0431; 0.0899 Water (Worst scenario) 0.0170 0.0067; 0.0274
Intercept 0.1587 0.0866; 0.23080.0964
Intercept 0.1786 0.1050; 0.25210.0667
Water (Best scenario) 0.1231 0.0792; 0.1670 Water (Best scenario) 0.0591 0.0338; 0.0844
Intercept 0.2318 0.1650; 0.2987 0.0501 Intercept 0.2295 0.1613; 0.2977
0.0465Windowsill dust loading 0.0003 0.0001; 0.0004 Windowsill dust loading
0.0033 0.0015; 0.0051
Intercept 0.2412 0.1761; 0.30640.0294
Intercept 0.2440 0.1793; 0.30880.0277
Floor dust loading 0.0022 0.0007; 0.0036 Floor dust loading 0.0243 0.0078; 0.0408
2) Low values of R-squares (<9%) indicate that an exposure source taking alone is not enough to explain the variability observed in the log(BLL).
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Unadjusted linear effects of environmental lead on BLL
Cumulative lead exposure index † Cross-sectional measure of exposure ††
Estimate 95% CI R-Square Estimate 95%CI R-Square
Intercept 0.1459 0.0714; 0.22050.0986
Intercept 0.2116 0.1393; 0.28380.0353
Water (Worst scenario) 0.0665 0.0431; 0.0899 Water (Worst scenario) 0.0170 0.0067; 0.0274
Intercept 0.1587 0.0866; 0.23080.0964
Intercept 0.1786 0.1050; 0.25210.0667
Water (Best scenario) 0.1231 0.0792; 0.1670 Water (Best scenario) 0.0591 0.0338; 0.0844
Intercept 0.2318 0.1650; 0.2987 0.0501 Intercept 0.2295 0.1613; 0.2977
0.0465Windowsill dust loading 0.0003 0.0001; 0.0004 Windowsill dust loading
0.0033 0.0015; 0.0051
Intercept 0.2412 0.1761; 0.30640.0294
Intercept 0.2440 0.1793; 0.30880.0277
Floor dust loading 0.0022 0.0007; 0.0036 Floor dust loading 0.0243 0.0078; 0.0408
3) Significant crude association between Log(BLL) and Water lead, Windowsill dust loading and Floor dust loading
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Adjusted linear effects of CLEI on BLL
1) Water lead and windowsill dust remain markedly associated with Log(BLL) (β=0.0758, p=0.0002 and β=0.0002, p=0.0058 respectively).
Unstandardized estimate
95% CI Standardized estimate
95% CI
Worst scenario
Intercept -0.0482 -0.9391; 0.8427 0.1747 -0.6928; 1.0421
Water 0.0758 -0.0359; 0.1156 0.1819 -0.1483; 0.4565
Windowsill dust loading 0.0002 -0.0001; 0.0004 0.0967 -0.0665; 0.3158
Floor dust loading 0.0007 -0.0014; 0.0028 0.0277 -0.0959; 0.1995
Paint lead
Reference level 0 0
Level-1 exposure 0.0735 -0.0885; 0.2356 0.0735 -0.0885; 0.2356
Level-2 exposure 0.2789 0.0599; 0.4979 0.2789 0.0599; 0.4979
Adjusted R-Square 0.2115
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Adjusted linear effects of CLEI on BLL
2) paint-lead effect was also strongly significant in children exposed to paint chips with high lead level (paint chips ≥ 5000 mg/kg) compared with those living in homes without paint chips and low lead level in painted surface (XRF < 1 mg/cm2).
Unstandardized estimate
95% CI Standardized estimate
95% CI
Worst scenario
Intercept -0.0482 -0.9391; 0.8427 0.1747 -0.6928; 1.0421
Water 0.0758 -0.0359; 0.1156 0.1819 -0.1483; 0.4565
Windowsill dust loading 0.0002 -0.0001; 0.0004 0.0967 -0.0665; 0.3158
Floor dust loading 0.0007 -0.0014; 0.0028 0.0277 -0.0959; 0.1995
Paint lead
Reference level 0 0
Level-1 exposure 0.0735 -0.0885; 0.2356 0.0735 -0.0885; 0.2356
Level-2 exposure 0.2789 0.0599; 0.4979 0.2789 0.0599; 0.4979
Adjusted R-Square 0.2115
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Adjusted linear effects of cross-sectional exposure on BLL
1) Water lead effect was no longer statistically significant (β=0.0106, p=0.0884).
Unstandardized estimate
95% CI Standardized estimate
95% CI
Worst scenario
Intercept 0.3656 -0.5196; 1.2508 0.4888 -0.3889; 1.3664
Water 0.0106 -0.0016; 0.0227 0.0598 -0.0091; 0.1288
Windowsill dust loading 0.0034 -0.0013; 0.0055 0.1079 -0.0404; 0.1754
Floor dust loading 0.0094 -0.0147; 0.0336 0.0322 -0.0502; 0.1146
Paint lead
Reference level 0 0
Level-1 exposure 0.1179 -0.0463; 0.2820 0.1179 -0.0463; 0.2820
Level-2 exposure 0.3008 0.0710; 0.5306 0.3008 0.0710; 0.5306
Adjusted R-Square 0.1557
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Adjusted linear effects of cross-sectional exposure on BLL
2) Adjusted R-square remains low by modeling cross-sectional exposure (0.1557 versus 0.2115 for CELI) .
Unstandardized estimate
95% CI Standardized estimate
95% CI
Worst scenario
Intercept 0.3656 -0.5196; 1.2508 0.4888 -0.3889; 1.3664
Water 0.0106 -0.0016; 0.0227 0.0598 -0.0091; 0.1288
Windowsill dust loading 0.0034 -0.0013; 0.0055 0.1079 -0.0404; 0.1754
Floor dust loading 0.0094 -0.0147; 0.0336 0.0322 -0.0502; 0.1146
Paint lead
Reference level 0 0
Level-1 exposure 0.1179 -0.0463; 0.2820 0.1179 -0.0463; 0.2820
Level-2 exposure 0.3008 0.0710; 0.5306 0.3008 0.0710; 0.5306
Adjusted R-Square 0.1557
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Association between CLEI (worst scenario) and BLL ≥ 2 µg/dl
Crude OR (95% CI) Adjusted OR (95% CI)
Model 1a Model 2b
Water (Worst scenario) (µg/kg of bw) < 1.12 1 1 1
1.12 - 2.92 1.20 (0.65 - 2.21) 0.69 (0.29 - 1.65) 1.11 (0.51-2.41)≥ 2.92 4.00 (2.41 - 6.65) 3.57 (1.74 - 7.32) 3.70 (1.93-7.11)
Windowsill dust loading (µg/kg of bw)
< 87.03 1 1 187.03 - 239.67 0.92 (0.49 - 1.73) 0.42 (0.16 - 1.10) 0.76 (0.35-1.72)
≥ 239.67 2.53 (1.55 - 4.15) 1.03 (0.45 - 2.37) 1.98 (1.03-3.82)Floor dust loading (µg/kg of bw)
< 8.12 1 1 18.12 - 20.47 2.09 (1.22-3.59) 3.64 (1.58 - 8.39) 1.97 (1.01-3.87)
≥ 20.47 2.44 (1.42-4.21) 3.44 (1.46 - 8.07) 2.25 (1.13-4.48)
Paint lead c
Reference level 1 1 1
Level-1 exposure 1.16 (0.68-1.97) 1.48 (0.65 - 3.37) 1.10 (0.56-2.14)Level-2 exposure 3.23 (1.78-5.84) 6.08 (2.21 - 16.71) 3.04 (1.44-6.42)
-2Log(Likelihood) 516.85 343.82
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Association between CLEI (worst scenario) and BLL ≥ 2 µg/dl
Crude OR (95% CI) Adjusted OR (95% CI)
Model 1a Model 2b
Water (Worst scenario) (µg/kg of bw) < 1.12 1 1 1
1.12 - 2.92 1.20 (0.65 - 2.21) 0.69 (0.29 - 1.65) 1.11 (0.51-2.41)≥ 2.92 4.00 (2.41 - 6.65) 3.57 (1.74 - 7.32) 3.70 (1.93-7.11)
Windowsill dust loading (µg/kg of bw)
< 87.03 1 1 187.03 - 239.67 0.92 (0.49 - 1.73) 0.42 (0.16 - 1.10) 0.76 (0.35-1.72)
≥ 239.67 2.53 (1.55 - 4.15) 1.03 (0.45 - 2.37) 1.98 (1.03-3.82)Floor dust loading (µg/kg of bw)
< 8.12 1 1 18.12 - 20.47 2.09 (1.22-3.59) 3.64 (1.58 - 8.39) 1.97 (1.01-3.87)
≥ 20.47 2.44 (1.42-4.21) 3.44 (1.46 - 8.07) 2.25 (1.13-4.48)
Paint lead c
Reference level 1 1 1
Level-1 exposure 1.16 (0.68-1.97) 1.48 (0.65 - 3.37) 1.10 (0.56-2.14)Level-2 exposure 3.23 (1.78-5.84) 6.08 (2.21 - 16.71) 3.04 (1.44-6.42)
-2Log(Likelihood) 516.85 343.82
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Association between CLEI (worst scenario) and BLL ≥ 2 µg/dl
Crude OR (95% CI) Adjusted OR (95% CI)
Model 1a Model 2b
Water (Worst scenario) (µg/kg of bw) < 1.12 1 1 1
1.12 - 2.92 1.20 (0.65 - 2.21) 0.69 (0.29 - 1.65) 1.11 (0.51-2.41)≥ 2.92 4.00 (2.41 - 6.65) 3.57 (1.74 - 7.32) 3.70 (1.93-7.11)
Windowsill dust loading (µg/kg of bw)
< 87.03 1 1 187.03 - 239.67 0.92 (0.49 - 1.73) 0.42 (0.16 - 1.10) 0.76 (0.35-1.72)
≥ 239.67 2.53 (1.55 - 4.15) 1.03 (0.45 - 2.37) 1.98 (1.03-3.82)Floor dust loading (µg/kg of bw)
< 8.12 1 1 18.12 - 20.47 2.09 (1.22-3.59) 3.64 (1.58 - 8.39) 1.97 (1.01-3.87)
≥ 20.47 2.44 (1.42-4.21) 3.44 (1.46 - 8.07) 2.25 (1.13-4.48)
Paint lead c
Reference level 1 1 1
Level-1 exposure 1.16 (0.68-1.97) 1.48 (0.65 - 3.37) 1.10 (0.56-2.14)Level-2 exposure 3.23 (1.78-5.84) 6.08 (2.21 - 16.71) 3.04 (1.44-6.42)
-2Log(Likelihood) 516.85 343.82
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Association between CLEI (worst scenario) and BLL ≥ 2 µg/dl
Crude OR (95% CI) Adjusted OR (95% CI)
Model 1a Model 2b
Water (Worst scenario) (µg/kg of bw) < 1.12 1 1 1
1.12 - 2.92 1.20 (0.65 - 2.21) 0.69 (0.29 - 1.65) 1.11 (0.51-2.41)≥ 2.92 4.00 (2.41 - 6.65) 3.57 (1.74 - 7.32) 3.70 (1.93-7.11)
Windowsill dust loading (µg/kg of bw)
< 87.03 1 1 187.03 - 239.67 0.92 (0.49 - 1.73) 0.42 (0.16 - 1.10) 0.76 (0.35-1.72)
≥ 239.67 2.53 (1.55 - 4.15) 1.03 (0.45 - 2.37) 1.98 (1.03-3.82)Floor dust loading (µg/kg of bw)
< 8.12 1 1 18.12 - 20.47 2.09 (1.22-3.59) 3.64 (1.58 - 8.39) 1.97 (1.01-3.87)
≥ 20.47 2.44 (1.42-4.21) 3.44 (1.46 - 8.07) 2.25 (1.13-4.48)
Paint lead c
Reference level 1 1 1
Level-1 exposure 1.16 (0.68-1.97) 1.48 (0.65 - 3.37) 1.10 (0.56-2.14)Level-2 exposure 3.23 (1.78-5.84) 6.08 (2.21 - 16.71) 3.04 (1.44-6.42)
-2Log(Likelihood) 516.85 343.82
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Unadjusted linear effectsAdjusted CLEI effectsAdjusted Cross-sectional effectsLikelihood of BLL ≥ 2 µg/dL
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Association between CS (worst scenario) and BLL ≥ 2 µg/dl
Crude OR (95% CI) Adjusted OR (95% CI)
Model 1a Model 2b
Water (Worst scenario) (µg/L)
< 2.16 1 1 1
2.16 - 4.96 1.51 (0.82 - 2.76) 1.48 (0.64 - 3.44) 1.40 (0.64 - 3.03)≥ 4.96 4.47 (2.64 - 7.57) 3.17 (1.50 - 6.71) 4.21 (2.16 - 8.19)
Windowsill dust loading (µg/ft2)
< 7.15 1 1 17.15 – 20.69 1.19 (0.65 - 2.17) 0.96 (0.41 - 2.26) 1.23 (0.53 - 2.38)
≥ 20.69 2.65 (1.61 - 4.36) 1.89 (0.88 - 4.04) 2.47 (1.30 - 4.69)Floor dust loading (µg/ft2)
< 0.70 1 1 1
0.70 - 1.62 2.20 (1.28 - 3.78) 1.60 (0.74 - 3.44) 1.95 (0.99 - 3.85)≥ 1.62 2.26 (1.31 - 3.88) 1.60 (0.73 - 3.51) 1.92 (0.96 - 3.84)
Paint lead c
Reference level 1 1 1
Level-1 exposure 1.14 (0.68 - 1.97) 0.93 (0.42 - 2.08) 1.08 (0.56 - 2.01)Level-2 exposure 3.23 (1.78 - 5.84) 4.48 (1.73 – 11.60) 3.04 (1.45 - 6.37)
-2Log(Likelihood) 517.95 352.50
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In the absence of cohort studies or Bone lead measures, cumulative lead exposure index is more appropriate than cross-sectional measures to estimate the association between lead exposure and Blood lead
In young children (aged under 6) included in this study:
If all other factors are kept stables, then for each additional increase in water cumulative exposure, BLL is expected to increase 1.08 µg/dl (p=0.0002).
If all other factors are kept stables, then for each additional increase in cumulative exposure of windowsill dust loading, BLL is expected to increase 1.00 µg/dl (p=0.0058).
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In the absence of cohort studies or Bone lead measures, cumulative lead exposure index is more appropriate than croiss-sectional measures to estimate the association between lead exposure and Blood lead
In young children (aged under 6) included in this study:
The mean BLL in children exposed to paint chips with high lead level (paint chips ≥ 5000 mg/kg) is 1.32 µg/dl higher than mean BLL observed in those living in homes without paint chips and low lead level in painted surface (XRF < 1 mg/cm2)
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INTRODUCTIONOBJECTIVES
METHODOLOGYRESULTS
CONCLUSIONS & PERSPECTIVES
35
In the absence of cohort studies or Bone lead measures, cumulative lead exposure index is more appropriate than croiss-sectional measures to estimate the association between lead exposure and Blood lead
In young children (aged under 6) included in this study:
1 unit of change in Cumulative floor dust loading does not markedly influence the BLL…However, floor dust loading is significantly associated with the odds of BLL ≥ 2 µg/dl from 8.12 µg/kg of body weight
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INTRODUCTIONOBJECTIVES
METHODOLOGYRESULTS
CONCLUSIONS & PERSPECTIVES
36
In the absence of cohort studies or Bone lead measures, cumulative lead exposure index is more appropriate than croiss-sectional measures to estimate the association between lead exposure and Blood lead
In young children (aged under 6) included in this study:
The odds of BLL ≥ 2 µg/dl is 4 times higher in children with water cumulative lead ≥ 2.92 µg/kg of bw when compared with those with water cumulative lead < 1.12 µg/kg of bw In the children under the present study, water lead is the first largest contributor to BLL, followed by paint-lead and windowsill dust loading.
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INTRODUCTIONOBJECTIVES
METHODOLOGYRESULTS
CONCLUSIONS & PERSPECTIVES
37
Future challenges :
Compare results obtained from cross-sectional measures of exposure with those reported in previous studies
Assess the departure from odds-ratio multiplicativity (and additivity) that may be due to nutritional factors , children’s characteristics and/or guardian’s socioeconomic position.
Translate cumulative lead exposure index in terms of public health languages (recommendations)
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Acknowledgment:
Canadian Water Network
Ministry of Environment and sustainable development (MDDEP)
Canada Health
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Research Team:Patrick LevalloisJulie St-LaurentDenis GauvinMarilène CourteauMichèle PrévostSchokoufeh NourFrance LemieuxMonique D’ArmourPat Rasmussen
Celine CampagnaElise DeshommesSuzanne GingrasAlain LeBlancAnnick Trudelle
THANK YOU !
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In the database we received, Paint lead was a categorical variable :
Reference level XRF < 1 mg/cm2
Level-1 exposure
XRF ≥ 1 mg/cm2 OR Paint chips < 5000 mg/kg
Level-2 exposure
Paint chip ≥ 5000 mg/kg
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Descriptive analysis of Environmental Exposure
Median (p25 – p75)
Water Lead (µg/dL)
WLLF5 1.24 (0.26 – 2.68)
WLLS1 2.33 (0.76 – 4.25)
WLLS2 2.24 (0.62 – 4.05)
WLLS3 1.99 (0.46 – 4.49)
WLLS4 1.90 (0.41 – 4.83)
Dust Lead (µg/ft2)
Floor dust 0.70 (0.35 – 1.62)
Windowsill dust 7.15 (2.56 – 20.70)