Neurocognitive Impairment Due to Early Life Arsenic Exposure

Size: px

Start display at page:

Download "Neurocognitive Impairment Due to Early Life Arsenic Exposure"

Randolf Simmons
5 years ago
Views:

1 Neurocognitive Impairment Due to Early Life Arsenic Exposure Joseph Graziano, PhD Professor of Environmental Health Sciences And Pharmacology Mailman School of Public Health Columbia University

2 Seminar Outline Background: Arsenicosis in Bangladesh Our Prospective Cohort Study in Adults Consequences of As Exposure in Children

3 History of Arsenic Problem in Bangladesh 1960 s 70 s 1 million tube wells installed by UNICEF 1970 s 80 s 3 4 million tube wells installed privately 97% of population drink tube well water Patients with arsenicosis diagnosed Arsenic detected in tube well water. 10 million tube wells now in use million people estimated to have been exposed Recognized as major public health problem 2000 Launch of the Health Effects of Arsenic Longitudinal Study (HEALS) Bangladesh government adopts a rural deep well drilling program

4 Tube wells are the major source of drinking water in Bangladesh and many other developing countries

5 Arsenic in Groundwater: An International Problem Taiwan China Chile Argentina Mexico United States India Bangladesh Nepal Vietnam Cambodia Mongolia Myanmar

6 Known Health Effects of Arsenic Early/Intermediate Skin Lesions: Melanosis Keratosis Other Conditions Diabetes mellitus Non pitting edema Non malignant respiratory disease Cognitive deficits** Black foot Disease Late Cancers: Skin Bladder Lung Liver Cardiovascular: Hypertension Ischemic Heart Disease**

9 BGS/DPHE (2001) Well As (ug/l)

10 0 Well As (ug/l) Depth (ft)

13 Arsenic in 5,966 wells

14 Cohort Recruitment and Follow-up: The HEALS Cohort 7/2000-5/2002 9/ / /2004-9/2006 6/2007-1/2009 Baseline Follow-up 1 Follow-up 2 Follow-up 3 HEALS Original Cohort ~12,000 adults 6/2006-8/ / / ~35,000 adults: HEALS original and Expanded cohort Baseline Follow-up 1 HEALS Expanded Cohort ~8,000 adults

15 Cohort Recruitment and Follow-up 113 deaths 120 deaths 174 deaths 7/2000-5/2002 9/ / /2004-9/2006 6/2007-1/2009 Baseline Follow-up 1 Follow-up 2 Follow-up 3 HEALS Original Cohort ~12,000 adults 6/2006-8/ / / ~35,000 adults: HEALS original and Expanded cohort Baseline Follow-up 1 HEALS Expanded Cohort ~8,000 adults A validated verbal autopsy was used to classify deaths using WHO s ICD-10

16 All cause and chronic disease mortality Table 2. Hazard ratio for mortality of HEALS participants in relation to baseline arsenic exposure, Bangladesh Arsenic exposure All-cause No. of mortality deaths No. of Chronic disease mortality * deaths HR 95% CI HR 95% CI Well water arsenic (μg/l) Referent Referent , , , , , , 2.33 P for trend Daily arsenic dose (μg/day) Referent Referent , , , , , , 2.18 P for trend Urinary total arsenic (μg/g Cr) Referent Referent , , , , , , 2.06 P for trend HR=hazard ratio; CI=confidence interval; Cr=creatinine. * Multivariate estimates adjusted for age, sex, body mass index, systolic blood pressure, education, and smoking status. Argos et al, Lancet 376: 252-8, 2010

20 During the summer of 1955, mass arsenic poisoning of bottle fed infants occurred in the western part of Japan because of contaminated milk powder. Environmental Health, 2006

21 This experience provides clear cut evidence for.developmental neurotoxicity. At the present time, more than 600 surviving victims, now in their 50s, have been reported to suffer from.mental retardation, neurological diseases and other disabilities. Environmental Health, 2006

23 Source: Bangladesh Rehabilitation Assistance Committee (BRAC)

24 80 Umbilical Cord Blood As (μg/l) A r=0.93 b= Maternal Blood As (μg/l) Hall et al, EHP 115: , 2007

27 Relationship Between Water Arsenic Concentrations and Intellectual Function Adjusted WISC III Raw Score Wasserman et al, EHP, 2004

28 Wasserman et al, EHP 2004

30 Mn by As interactions were not significant in adjusted or unadjusted models. Findings are consistent with other reports documenting adverse impact of both As and Mn exposure on child development outcomes.

34 The provision of deep, low arsenic tube wells, coupled with education, lowered biomarkers of exposure (measured after two years): Conclusions: A greater decrease in UAs/Cr was associated with significantly greater improvements in WISC IV Working Memory scores, but NOT with a greater improvement in other scores. Wasserman et al, EHP, 2016

35 Elevated groundwater arsenic from natural sources USGS, 2003 About 30,000 monitoring wells

36 Arsenic concentrations in 1,428 domestic wells from 17 towns in central Maine, with 31% of the wells containing > 10 ug/l [As] (source: Yang 2010).

37 Environmental Health, 2014

38 Estimating IQ points lost* attributable to water arsenic, comparing those with WAs >5 ppb vs WAs <5ppb Full Scale IQ: 4.0 (CI 6.8, 1.2); p<0.01 Perceptual Reasoning: 4.4 (CI 7.4, 1.4); p<0.01 Working Memory: 3.5 (CI 6.6, 0.3); p<0.05 Verbal Comprehension: 3.1 (CI 6.7, 0.5); p<0.10 *Adjusted for mother s IQ and education, HOME scores, number of siblings and school district. Wasserman et al, Environ Health, 2014

39 Arsenic in 5,966 wells

40 Ongoing: Lifetime Exposure and Health Outcomes in Adolescents HEALS Inclusion criteria Baseline Follow up 1 Follow up 2 Follow up 3 Follow up 4 Mom This study Child Outcomes: WISC IV, CANTAB, PFTs

41 Mother s water arsenic exposure over time 250 Water arsenic (ug/l) N Baseline Baseline Follow up 1 1Follow up Follow up3 200 Low, 3.0 Low, 2.9 Low, 2.9 Low, Mod, 26.5 Mod, 26.2 Mod, 26.3 Mod, High, High, High, High, High, Mod, 13.8 Mod, 12.1 Mod, 12.1

42 Selected Characteristics of the Adolescent Study WAs<10 µg/l n = 200 WAs 10 50µg/L n = 246 WAs>50 µg/l n = 192 Measures Mean ±SD or % (n) Mean ±SD or % (n) Mean ±SD or % (n) p value Child characteristics Male (%) 46 (92) 43.9 (108) (88) Child age (years) ± ± ± Years in school 6.78 ± ± ± Currently attending school (%) 84.9 (169/199) 86.1 (210/244) 80.2 (154) Exposure characteristics Prenatal well water As (µg/l) Concurrent well water As (µg/l) 3.2 ± ± ± ± ± ± 93.3 <.0001 Biological measures n = 194 n = 243 n = 187 UAs (µg/l) 37.1 ± ± ± <.0001 UAs/Cr (µg/g Cr) 81.3 ± ± ±324.1 <.0001 n = 195 n = 243 n = 185 BMn (µg/l) 11.8 ± ± ± BAs (µg/l) 2.5 ± ± ± 6.5 <.0001 BPb (µg/dl) 10.6 ± ± ± BCd (µg/l) 0.7 ± ± ±0.2 <.0001 BSe (µg/l) ± ± ±

43 Selected Characteristics of the Study Participants WAs<10 µg/l n = 200 WAs 10 50µg/L n = 246 WAs>50 µg/l n = 192 Measures Mean ±SD or % (n) Mean ±SD or % (n) Mean ±SD or % (n) p value Child characteristics Male (%) 46 (92) 43.9 (108) (88) Child age (years) ± ± ± Years in school 6.78 ± ± ± Currently attending school (%) 84.9 (169/199) 86.1 (210/244) 80.2 (154) Exposure characteristics Pre natal well water As (µg/l) Concurrent well water As (µg/l) 3.2 ± ± ± ± ± ± 93.3 <.0001 <.0001 Biological measures n = 194 n = 243 n = 187 UAs (µg/l) 37.1 ± ± ± <.0001 UAs/Cr (µg/g Cr) 81.3 ± ± ± <.0001 n = 195 n = 243 n = 185 BMn (µg/l) 11.8 ± ± ± BAs (µg/l) 2.5 ± ± ±6.5 <.0001 BPb (µg/dl) 10.6 ± ± ± BCd (µg/l) 0.7 ± ± ±0.2 <.0001 BSe (µg/l) ± ± ±

44 Selected Characteristics of the Study Participants WAs<10 µg/l n = 200 WAs 10 50µg/L n = 246 WAs>50 µg/l n = 192 Measures Mean ±SD or % (n) Mean ±SD or % (n) Mean ±SD or % (n) p value Child characteristics Male (%) 46 (92) 43.9 (108) (88) Child age (years) ± ± ± Years in school 6.78 ± ± ± Currently attending school (%) 84.9 (169/199) 86.1 (210/244) 80.2 (154) Exposure characteristics Pre natal well water As (µg/l) Concurrent well water As (µg/l) 3.2 ± ± ± ± ± ± 93.3 <.0001 <.0001 Biological measures n = 194 n = 243 n = 187 UAs (µg/l) 37.1 ± ± ± <.0001 UAs/Cr (µg/g Cr) 81.3 ± ± ± <.0001 n = 195 n = 243 n = 185 BMn (µg/l) 11.8 ± ± ± BAs (µg/l) 2.5 ± ± ±6.5 <.0001 BPb (µg/dl) 10.6 ± ± ± BCd (µg/l) 0.7 ± ± ±0.2 <.0001

45 Selected Characteristics of the Study Participants WAs<10 µg/l n = 200 WAs 10 50µg/L n = 246 WAs>50 µg/l n = 192 Measures Mean ±SD or % (n) Mean ±SD or % (n) Mean ±SD or % (n) p value Child characteristics Male (%) 46 (92) 43.9 (108) (88) Child age (years) ± ± ± Years in school 6.78 ± ± ± Currently attending school (%) 84.9 (169/199) 86.1 (210/244) 80.2 (154) Exposure characteristics Pre natal well water As (µg/l) Concurrent well water As (µg/l) 3.2 ± ± ± ± ± ± 93.3 <.0001 <.0001 Biological measures n = 194 n = 243 n = 187 UAs (µg/l) 37.1 ± ± ± <.0001 UAs/Cr (µg/g Cr) 81.3 ± ± ± <.0001 n = 195 n = 243 n = 185 BMn (µg/l) 11.8 ± ± ± BAs (µg/l) 2.5 ± ± ±6.5 <.0001 BPb (µg/dl) 10.6 ± ± ± BCd (µg/l) 0.7 ± ± ±0.2 <.0001

46 Adjusted Full Scale WISC Raw Scores by Group 190 Adjusted Full Scale Raw Score Group 1 Group 2 Group 3 Group 4 (Low WAs) (Mod WAs) (Hi WAs) (Hi Mod WAs)

47 Adjusted Change in Raw Scores by Quartiles of Urine Arsenic and Blood Arsenic Full Scale Raw Score Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Urine Arsenic (µg/g) Creatinine Blood Arsenic (µg/l) UAs/Cr range by quartile (15.8, 58.1) (58.1, 104.2) (104.2, 191.9) (191.9, ) BAs range by quartile (0.75, 2.18) ((2.18, 3.50) (3.50, 5.85) (5.85, 50.91) After adjustment for mother s IQ, father s education, BPb, BCd, BMn housing type, child s years of education, head circumference, and group. Working Memory subscale drives the finding.

48 Summary and Conclusions 1. We have repeatedly observed adverse associations between well water As exposure and child intelligence in young children in Bangladesh. 2. We observed similar findings in 3rd 5th grade children drinking As contaminated water in Maine. 3. In Bangladesh, the provision of deep, low As tubewells, coupled with education, was effective in substantially lowering biomarkers of As exposure, but after two years, only Working Memory had improved. 4. Among adolescents whose early life water As exposure was well characterized, concurrent biomarkers of As exposure were significantly associated with decrements in Full Scale raw scores on the WISC IV. This finding was driven by adverse associations between As biomarkers and the Working Memory subscale.

49 Acknowledgements In the United States Gail Wasserman Xinhua Liu Diane Levy Nancy LoIacono Faruque Parvez Pam Factor Litvak Jennie Kline Vesna Slavkovich Jagoda Balac David Santiago Lex van Geen Tyler Ellis Yan Zheng Habibul Ahsan (Univ. Chicago) Yu Chen (NYU) In Bangladesh Tariqul Islam Hasan Shahriar Mohammed Uddin Abu Siddique Samiul Islam Rebeka Sultana Ruksana Sultana Abul Kamal Samsuddin Golam Sarwar Study Participants Superfund Research Program grant P42 ES 10349; NIEHS Center Grant P30 ES Water Aid Bangladesh

50 Thank You

Jieying Jiang, Ph.D. Yu Chen, Ph.D., MPH Habibul Ahsan, M.D., MMedSc

Jieying Jiang, Ph.D. Yu Chen, Ph.D., MPH Habibul Ahsan, M.D., MMedSc Emerging Epidemic of CVD in Developing Countries Developed countries Relative contribution of CVD deaths to total mortality in 1990