Prevention Paradox. Why a Little Lead is Too Much

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1 Prevention Paradox Why a Little Lead is Too Much Bruce Lanphear, MD, MPH Child & Family Research Institute, BC Children s Hospital Faculty of Health Sciences Simon Fraser University

2 Binder S, Falk H. Strategic plan for the elimination of childhood lead poisoning. Atlanta: Centers for Disease Control, 1991.

3 Percent of Preschool Children Exceeding Selected Blood Lead Levels, NHANES II - III Percent of Children Pirkle JL, et al. Environ Health Perspect 1998;106: Year

4 Blood Lead Levels > 10 µg/dl among Children in Rochester, 1995 Percent > 10 µg/dl < > 50 Non-residential

5 Low-level Lead Exposure and Cognitive Deficits

6 Reading Scores by Blood Lead Levels in US Children, NHANES III, Adapted from Lanphear BP, et al. Public Health Reports 2000;115:

7 Verb Generation Task by Lifetime Mean Blood Lead Concentration (n=42) Low Lifetime Mean Blood Lead (7.6 μg/dl) High Lifetime Mean Blood Lead (26 μg/dl) Yuan W, et al. Pediatrics 2006;118:

8 Lead Toxicity at Blood Lead Levels <10 µg/dl Canfield, et al. NEJM 2003;348:

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11 Research Supporting Adverse Cognitive Effects at Blood Lead Levels < 10 µg/dl Chiodo LM, et al. Neurodevelopmental effects of postnatal lead exposure at very low levels. Neurotoxicol Teratol 2004;26: Kordas K, et al. Deficits in cognitive function and achievement in Mexican first-graders with low blood lead concentrations. Environ Res 2006;100: Tellez-Rojo MM, et al. Longitudinal associations between blood lead concentrations lower than 10 µg/dl and neurobehavioral development in environmentally exposed children in Mexico City Pediatrics. 2006;118:e Hu H, et al. Fetal lead exposure at each stage of pregnancy as a predictor of infant mental development. Environ Health Perspect 2006;114: Sarkin PJ, et al. Neuropsychological function in children with blood lead levels below 10 µg/dl. Neurotoxicology 2007;28: Solon O, et al. Associations between cognitive function, blood lead concentration and nutrition among children in the Central Philippines. Journal of Pediatrics 2008;152: Chiodo LM, et al. Blood lead levels and specific attention effects in young children. Neurotoxicol Teratol 2007;29: Chandramouli K, et al. Effects of early childhood lead exposure on academic performance and behavior of school age children. Arch Dis Child 2009;94: Min MO, et al. Cognitive development and low-level lead exposure in poly-drug exposed children. Neurotoxicol Teratol 2009:31: Jedrychowski W et al., Gender specific differences in neurodevelopmental effects of prenatal exposure to very low-lead levels: the prospective cohort study in three-year olds. Early Hum Dev. 2009:85:

12 Mean Adjusted Full-Scale IQ Scores by Quartiles for Tibial Bone Lead and Mean Lifetime Blood Lead Levels p < 0.01 p < 0.05 Full-Scale IQ Quartiles Wasserman GA, et al. Child Neuropsychol 2003;9:22-34.

13 Mean Adjusted Full-Scale IQ Scores by Quartiles for Tibial Bone Lead and Average Lifetime Blood Lead Levels Combined Analysis p < 0.01 p = NS Full-Scale IQ Quartiles Wasserman GA, et al. Child Neuropsychol 2003;9:22-34.

14 Body Burdens of Lead in Ancient Peoples, Typical American and Overt Lead Poisoning

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16 The Prevention Paradox The majority of disease and disability occurs in people who are at low to moderate risk

17 Adapted from Bellinger D. EHP 2011;120:

18 High-Risk or Low-Risk Strategy?

19 Low-level Toxicity

20 Reading Scores by Serum Cotinine in US Children, NHANES III, p=0.02 Yolton K, et al. Environ Health Perspect 2005;113:

21 Mean adjusted birth weight by third-trimester urinary cotinine concentration (n = 2,481) England, L. J. et al. Am. J. Epidemiol : ; doi: /aje/

22 Daily Mortality in London for Winters ( ) by Particulate Air Pollution (British Smoke) Pope CA, et al. Circulation. 2009;120:

23 Risks of Ischemic Heart Disease, CVD and Cardiopulmonary Disease Mortality by Cigarette Smoke Pope CA, et al. Circulation. 2009;120: (IHD=gray, CVD=dark gray and CPD=black)

24 Exposure Response Relationship for Benzene and Leukemia: A Meta-analysis Vlaanderen J, et al. Env Health Perspect 2010;118:

25 No Acceptable Levels?

26 Low-Level Lead Toxicity and Psychopathology

27 Needleman HL, et al. N Engl J Med 1979;300:

28

29 Gray Matter Loss by Childhood Lead Exposure Adjusted for child s age, birth weight. Sex, gestational age, IQ, prenatal tobacco, prenatal alcohol, prenatal marijuana, total intracranial volume, SES and HOME Inventory did not alter results (Cecil K, PLoS Medicine, et al. 2008).

30 Key Imaging Findings in ADHD Brain areas with reduced size in ADHD Frontal cortex Prefrontal Cingulate cortex Basal ganglia - striatum Caudate, putamen Cerebellum Giedd et al., 2001; Seidman et al., 2005

31 Reduction in Gray Matter by Childhood Blood Lead Levels and Subject s Sex Men (n=83) Women (n=74) Adjusted for child s age, birth weight. Sex, gestational age, IQ, prenatal tobacco, prenatal alcohol, prenatal marijuana, total intracranial volume, SES and HOME Inventory did not alter results (Cecil K, Brubaker C, Dietrich KN, et al. PLoS Medicine 2008).

32 Tooth Lead Levels and Criminality Number Self-reported offenses Tooth Lead Levels (ppb) Convictions Fergusson D, et al. J Epidemiol Community Health 2008;62: Adjusted for SES, maternal education, ethnicity, family conflict, maltreatment, maternal smoking during pregnancy, parental criminal offending and parental alcoholism.

33 8 No. of Arrests by Childhood Lead Exposure The Cincinnati Lead Study 6 No. of Arrests 4 2 Males Females Six-Year Blood Lead Levels (µg/dl) Wright J, PLoS Med 2008;5:e101.

34 Risk of Conduct Disorder by Blood Lead Concentration in US Children, 8 to 15 years, NHANES Adjusted Odds Ratio Blood Lead (µg/dl) Braun J, et al. Environ Health Perspect 2008;116:

35 Cervantes MC, et al. Dev Psychobiol 2005;47:

36 Lead Exposure and Murder Rate (/100,000) in the United States Nevin R. Environmental Research 2000:83;1-22

37 Cost-Benefit of Reducing Childhood Lead Exposure

38 $1= $17 to 220 Gould E. EHP 2009;117:

39

40 $977 Billion Attina TM, et al. EHP 2013;121:

41 Implications for Prevention Eliminate all non-essential uses of lead worldwide and develop regulations to control lead emissions Establish empirically-derived health-based standards for lead in air, house dust, soil and water Screen housing units for lead hazards before purchase or occupancy, after renovation and abatement Lower level of concern to < 1µg/dL and set new goals to achieve population levels with adequate margin of safety Lower action level to 5 µg/dl and begin environmental interventions at lower blood lead level

42 "All scientific work is incomplete whether it be observational or experimental. All scientific work is liable to be upset or modified by advancing knowledge. That does not confer upon us a freedom to ignore the knowledge we already have, or to postpone the action that it appears to demand at a given time. Austin Bradford Hill Hill AB. Proc Royal Soc Med 1965;58:

Systematic Review of Low Blood Lead Levels and Associations with Cognitive and Neuro-behavioral Outcomes in Children (Abridged Version)

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