Maryse Bouchard, PhD

Transcription

1 Maryse Bouchard, PhD Researcher Research Center CHU Sainte-Justine University of Montreal Adjunct Professor, CINBIOSE, University of Quebec at Montréal

2 Highest concentrations found in groundwater In the U.S. and Canada, 20-30% of the population consumes groundwater Dissolution of manganese from minerals in contact with water Concentration depends on local geological characteristics and physico-chemical conditions Concentrations vary by several orders of magnitude Surface water (lake and rivers): up to 200 ug/l (rare)

3 Exposure by ingestion is generally considered harmless because of low systemic absorption Studies have shown neurotoxic effects associated to exposure through inhalation, mostly with occupational exposures Some data on children suggestives of adverse effects with exposure from water

4 In China 1 : 90 children (11-13 y) exposed ug/l Mn in water were compared to matched-pair referents: Mn in hair Digit Span, Digit Symbol, Benton Visual Retention, Pursuit Aiming, and Santa Ana; scores correlate with hair Mn In Bangladesh 2 : 142 children (10 y) exposed to Mn in water ( µg/l; mean 795 µg/l) IQ with concentration of Mn in well water 1 He et al 1994, 2 Wasserman et al 2007

5 In Quebec : 46 children (6 15 y) exposed to ug/l Higher water Mn associated to higher hair Mn Higher hair Mn associated with increased frequency of teacherreported hyperactive and oppositional behaviours Hyperactivity (score adjusted for income and age) Mn hair (ug/g) Bouchard et al Environ Health Persp

6 Funding: Canadian Institutes for Health Research Principal investigators: Bouchard & Mergler Multidisciplinary team Engineer in water treatment: Benoit Barbeau (Industrial Chair in Drinking Water, Polytechnic School, Montreal) Chemist: Sébastien Sauvé (University of Montreal) Neuropsychologist: Élyse Limoges (Hotel Dieu de Québec) Developmental psychologist : Thérèse Bouffard (University of Quebec at Montreal) Nutritionist: Mélissa Legrand (Health Canada) Epidemiologist/neuropsychologist: David Bellinger (Harvard School of Public Health) 6

7 Choice of study sites Communities using groundwater 8 communities chosen to form gradient of Mn concentrations Study group Recruitment through primary schools (June 07 - June 09) Participation rate 25 37% Inclusion criteria: child lives in current house > 3 months 362 children (6-13 years)

8 Quebec city Montreal 50 mi

9 Cognitive tests Wechsler Abbreviated Scale of Intelligence (WASI): IQ Memory: California Verbal Learning Test Children's Version (CVLT C) Inhibition: D-KEFS Color-Word Interference Test Attention/impulsivity: Conners' Continuous Performance Test II (CPT-II) Motor tests Items from the Luria Nebraska Motor Scale Manual dexterity: Santa Ana Motor speed: Fingertapping Questionnaires administered to parent and teacher Conners Rating Scales (long form; revised version) School motivation, psychosocial adaptation and school performance

10 Structured Interview with mothers: Socioeconomic status: maternal education, family income Raven Progressive Matrices: non-verbal intelligence HOME: cognitive stimulation at home Child medical history, including perinatal stress and birth weight, etc. Exposure to neurotoxicants in utero and perinatally: alcohol, tobacco, lead, pesticides, etc.

11 Homes tap water sampling Measurement of Mn, Pb, Fe, Ca, Cu, Zn, As, Mg (ICP-MS) Children hair sampling 2 cm closer to the scalp (=exposure from 3-4 last months) Measurement of Mn, Pb, Fe, Cu, Zn, As (ICP-MS) Assessment of dietary intake of manganese and iron Food frequency questionnaire; Assessment of intake of tap water, through drinking and incorporation into food preparations Residency history: Length of exposure to current manganese levels

12 Generalized Estimating Equations Extension of generalized linear models for non-independent data Accounts for the community- and family-clustered data in our study (n=362 children from 251 families from 8 communities) Choice of covariates based on the literature and the relations observed in our dataset: o age and sex of children o maternal intelligence & education o family income & structure o HOME score o iron water concentration

13 Frequency % Water Mn (Geo. mean) P Value Home tap water source b <0.001 Private well % 8 Aqueduct (public well) % 55 Child s sex a 0.71 Boys % 19 Girls % 21 Family income b 0.28 $50,000 and less % 27 More than $50, % 20 Maternal education b 0.86 High school diploma or less 55 22% 20 Some college % 24 Some university 80 32% 21 Non-verbal maternal intelligence b Less than % 26 a One measure per child (n=362); b One measure per 94 family 38% (n=251) 20 More than %

14 Median: 34 ug/l Organoleptic norm (50 ug/l) Mean: 97 ug/l SD: 210 ug/l Range: ug/l WHO Guideline (400 ug/l) 4 values > 500 ug/l

15 A 30% of children reported not drinking tap water However, 96% of families used tap water in food preparation 50% of total Mn intake from water was from water incorporated into food preparation Pearson correlation of Mn in water with other elements : 0.68 (Fe), 0.26 (Zn), 0.11 (Cu), 0.06 (As), and (Pb) Water Mn concentration from 3 repeated sampling in the same residence over a period of 1 year had an intra class correlation coefficient of 0.91: Mn is stable across 1 year.

16 Diet Water Bouchard et al. Environmental Health Perspectives (in press) Sept. 20, 2010

17 Unadjusted model Adjusted model a Full scale IQ -3.2 (-6.2, -0.2)* -3.3 (-6.1, -0.5)* Performance IQ -2.5 (-5.7, 0.8) -2.8 (-5.9, 0.4) Verbal IQ -2.8 (-5.6, 0.5) -2.7 (-5.4, 0.1) * P 0.05, ** P 0.01 a Child s sex and age, maternal intelligence and education, family income, home stimulation score, family structure, IQ testing session, source of water and water Fe. Bouchard et al. Environmental Health Perspectives (in press) Sept. 20, 2010

18 Unadjusted model Adjusted model B a Full scale IQ -2.1 (-3.5, -0.8)** -2.4 (-3.9, -0.9)** Performance IQ -2.4 (-4.0, -0.7)** -3.1 (-4.9, -1.3)** Verbal IQ -1.4 (-2.6, -0.2)* -1.2 (-2.7, 0.3) * P 0.05, ** P 0.01 a Child s sex and age, maternal intelligence and education, family income, home stimulation score, family structure, IQ testing session, source of water and water Fe. Bouchard et al. Environmental Health Perspectives (in press) Sept. 20, 2010

19 Adjusted Verbal IQ Water manganese concentration (ug/l) IQ is plotted by median of water Mn quintiles.

20 Adjusted Performance IQ Water manganese concentration (ug/l) IQ is plotted by median of water Mn quintiles.

21 Adjusted Full Scale IQ Δ6.6 points Concentration of manganese in water (ug/l)

22 Adjusted immediate recall * For a 10-fold increase : B= (SE 0.11) P ,000 Water manganese concentration (ug/l) *California Verbal Learning Test for Children

23 Adjusted score delayed recall* For a 10-fold increase : B= (SE 0.11) P ,000 Water manganese concentration (ug/l) *California Verbal Learning Test for Children

24 Motor coordination (Santa Ana test) 17.0 For a 10-fold increase : B= (SE 0.13) P ,000 Tap water manganese concentration (ug/l)

25 Amount of Mn from water <<< diet, but only water Mn is associated with increased hair Mn content & IQ scores suggests that Mn exposure from drinking water is metabolized differently than that from the diet Water Mn significantly associated to Full Scale IQ Association very robust to confounders adjustment Children in the highest water Mn decile (median: 267 µg/l) scored 6.6 IQ points below those least exposed. Previous studies reported cognitive deficits with high levels in water (He et al, 2004; Wasserman et al, 2006) Here, much lower level: above WHO guideline for 4% of the group

26 Timing of exposure (cross-sectional study) Past exposure responsible for observed association? Exposure misclassification Contribution of Mn exposure from water consumed outside the home? Residual external contamination of hair Levels of Mn concentration in water not representative of the rest of Canada or the U.S. But levels associated with effects not uncommon; e.g. in New Brunswick, 40% of wells > 50 µg Mn/L

27 Our findings suggest that the current consensus that Mn in water is harmless should be reconsidered. These findings should be replicated Next: Risk assessment analyses using benchmark-dose approach to identify Mn levels with acceptable risk Visualization of brain accumulation of Mn with MRI; pilot study on 10 children with high / 10 low exposure Approximately 50% of the children are now exposed to Mn levels, follow-up study would inform on reversibility of cognitive impairments (grant application submitted CIHR fall 2010)

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29 Full scale IQ Manganese concentration in hair (ug/g) Adjusted for child s sex and age, maternal intelligence and education, family income, home stimulation score, family structure, IQ testing session, source of water and water Fe.