# Presentation: 917244

## A Study of the Health Effects of Children’s Exposure to Prevalent Neurotoxicants in an Urban Community

**A Study of the Health Effects of Children’s Exposure to Prevalent Neurotoxicants in an Urban Community**
- Chris Saint1, Bruce P. Lamphear2 (Presented by: Susan Laessig1)
- 1 US Environmental Protection Agency, NCER, 2 Cincinnati Center for Children’s Environmental Health, Cincinnati Children’s Hospital.

- Children living in urban environments are potentially more highly exposed to prevalent neurotoxicants such as lead, mercury, pesticides, polychlorinated organic compounds, and environmental tobacco smoke. The Cincinnati Children’s Environmental Health Center (CCEHC) at the Cincinnati Children’s Medical Center is conducting ORD-sponsored research through a Science-To-Achieve-Results (STAR) Program center grant to address the links between children’s exposure to chemicals and adverse neurobehavioral effects1.

**Research Goals**

**Methods/Approach**

**Science Question**

**Impact and Outcomes**

**Results/Conclusions**

**Future Directions**

- These studies will provide better measures of exposure to neurotoxicants and the simultaneous evaluation of the adverse effects of exposures to multiple prevalent toxicants in the human population during early childhood. A better understanding of the remote behavioral effects of early toxicant exposure will lead to the development of primary prevention methods (both environmental and cognitive/ educational) that will alter the developmental trajectories of large numbers of exposed children. The research will provide tools for families and communities to identify environmental neurotoxicants and disseminate information by establishing the Healthy Home Resource Center at the Better Housing League. The results of this project will also stimulate community - wide prevention efforts and exposure assessment by participants in population-based studies.

**References**

- Baghurst PA, et. al. Pediatric and Perinatal Epidemiology 1992; 6: 403-15; Bellinger DC, et.al. Pediatrics 1992: 90: 855-61; Grandjean P, et. al. Monograms of the American Association of Metal Health 1987; 8:71-95; Jacobsen JL, et. al. New England Journal of Medicine 1996; 335:783-9.
- 2. 	Lanphear BP, Howard C, Eberly S, Auinger P, Kolassa J, Weitzman M, Schaffer SJ, Alexander K.  Primary prevention of childhood lead exposure: A randomized trial of dust control.  Pediatrics. 1999; 103 (4 Pt 1): 772-7.
- Willet W.  Nutritional Epidemiology, New York.  Oxford University Press, 1990.
- Gordon SM, Callahan PJ, Nishioka MG, Brinkman MC, O'Rourke MK, Lebowitz MD, Moschandreas DJ.  Residential environmental measurements in the national human exposure assessment survey (NHEXAS) pilot study in Arizona: preliminary results for pesticides and VOCs. J Expo Anal Environ Epidemiol. 1999; 9(5): 456-470.
- Cadwell BM.  Home Observation for the Measured Environment.  Little Rock, AK.  University of Arkansas at Lilttle Rock, 1984.
- Hu YA, Barr DB, Akland G, Melnyk L, Needham L, Pellizzari ED, Raymer JH, Roberds JM.  Collecting urine samples from young children using cotton gauze for pesticide studies.  J Expo Anal Environ Epidemiol. 2000;10(6 Pt 2): 703-709.
- Bearer CF.  Meconium as a biological marker of prenatal exposure.  Ambul Pediatr. 2003; 3(1): 40-43.
- AGS - Peabody PictureVocabulary Test - Third Edition.  Circle Pines, MN: American Guidance Services, Inc., 1992.
- Beck, AT.  Beck Depression Inventory - II.  San Antonio, TX. The Psycological Corporation, 1996.
- Abidin RR.  Pareting Stress Index - Third Edition.  Odessa, Fl.  Pscyological Assessment, Inc., 1995.
- The Psycological Corporation.  Bayley Scales for Infant Development - Second Edition.  San Antonio, TX. The Psycological Corporation, 1993.
- Reynolds CR, kamphaus, RW.  Behavioral Assesment for Children.  Circle Pines, MN: American Guidance Services, Inc., 1992
- Elliot E.  Differential Ability Scales.   San Antonio, TX. The Psycological Corporation, 1990.
- Espy KA, Kaufmann PM, McDiarmid MD, Glisky ML.  Executive functioning in preschool children: performance on A-not-B and other delayed response format tasks.  Brain Cogn. 1999; 41(2): 178-199.
- Kahn RS, Khoury J, Nichols WC, Lanphear BP.  Role of dopamine transporter genotype and maternal prenatal smoking in childhood hyperactive-impulsive, inattentive, and oppositional behaviors.  J Pediatr. 2003; 143(1): 104-110
- Yolton K, Dietrich K, Auinger P, Lanphear BP, Hornung R. Exposure to Environmental Tobacco Smoke and Cognitive Abilities among U.S. Children and Adolescents. Environ Health Perspect. 2005; 113 (1): 98-103.

- Are developmental disorders, behavioral problems, growth retardation, and hearing loss in children associated with exposures to environmental toxicants?
- Are adverse changes in brain function and morphology associated with exposure to environmental toxicants and/or the neurobehavioral effects potentially associated with these exposures?
- How safe and efficacious are the various methods used to reduce exposures to prevalent environmental toxicants?

- The CCEHC is an interdisciplinary organization with each component contributing to the overall goal. All of the five research projects in the Center focus on the linkage of exposures to prevalent environmental toxicants with neurobehavioral outcomes.
-    Identify and define causes of developmental disorders, behavioral problems, growth retardation and hearing loss due to environmental toxicants.
-    Develop and validate biomarkers for *in utero* exposures and environmental monitoring methods for exposure and risk characterization.
-    Use rigorous epidemiologic methods to test the safety and efficacy of interventions to reduce exposures to prevalent environmental toxicants.
-    Identify adverse effects of lead exposure on social functions, delinquent behaviors and incarceration, conduct disorders, and features consistent with ADHD in early adulthood.
-    Assist community members to identify and ultimately protect their children from adverse effects linked with environmental toxicants.

- The CCEHC will continue to recruit and collect data from the HOME cohort during 2005.  They will also begin data analysis of the biomarker and outcome data during this time.  These analyses should be completed during 2006.

**PROJECT 5. "MR ASSESSMENT OF BRAIN FUNCTION ALTERED BY LEAD EXPOSURE“**
**Purpose: **to better understand the relationship of environmental lead exposure with alterations in brain neurochemistry, structure, and function using magnetic resonance methods.
-    Advanced *in vivo* Magnetic Resonance (MR) methods will be used in approximately 150 subjects from the CLS.
-    Measurements include metabolite concentrations (N-acetyl aspartate, creatine, choline, and myo-inositol), total brain volume, volumes of cortical gray matter, white matter, and sub-structures within the basal ganglia.
- Functional MRI will be used to measure levels of brain activation during semantic language tests, working memory, and attention tests in 40 subjects with a childhood history of lead exposure.

**PROJECT 1. "NEUROBEHAVIORAL EFFECTS OF PREVALENT TOXICANTS IN CHILDREN" **
**Purpose: **to assess the risks of environmental exposures during two critical developmental phases: *in utero* and in early childhood.
-   The Health Outcomes and Measures of the Environment (HOME)** **cohort study of 400 children will examine the relationship between low-level exposures to prevalent neurotoxicants and behavioral problems which includes a nested, randomized controlled trial of lead hazard abatement.
-   A stratified sampling scheme based on population density and median income of the census tract of the residence will obtain a broad representation in terms of urban/rural status, socioeconomic status, and race/ethnicity.
-   The cohort will be randomized into a control group and a Lead Hazard Group (intervention) based on the levels of lead in various environmental samples  (Figure 1).  A nested, randomized, single blinded, prospective design will be conducted to investigate the efficacy of lead hazard abatement in preventing childhood lead exposure.
-   The HOME study cohort will be used to collect an extensive amount of information on childhood exposure to environmental toxicants and the adverse health outcomes they may cause (Table 1).
-   Gene-environment interactions can be examined in cooperation with the NIEHS-funded Center for Environmental Genetics.
-   A national survey of effects of neurotoxicant exposure is being conducted using data from the National Health and Nutrition Examination Survey (NHANES III) to study the relationship between lead and ETS exposure and cognitive abilities among U.S. children aged 6-16 years of age.

**PROJECT 2. "VALIDATION OF MECONIUM MARKERS OF FETAL NEUROTOXICANT EXPOSURES" **
**Purpose: **to test the hypothesis that meconium samples can be used for simultaneous analysis of several different environmental neurotoxicants to which the fetus is exposed.
-    A technique will be developed to quantitatively analyze cotinine, lead, methyl mercury, organophosphate metabolites, pyrethrins, and ethanol metabolites in a single sample of meconium. Concentrations of toxicants and their metabolites in meconium will be compared to maternal and infant measures in the HOME study to determine the relationship between these markers and meconium markers.
-    These studies will provide preliminary data on the feasibility and utility of meconium analysis to gauge the influence of environmental neurotoxicants on human fetuses.

**PROJECT 4. "EARLY EXPOSURE TO LEAD AND ADULT ANTISOCIAL OUTCOME" **
**Purpose: **to examine the relationship between early prenatal and postnatal exposure to lead and antisocial behavior in adulthood.
-    Follow-up of 280 participants in the Cincinnati Lead Study (CLS), a birth cohort whose development and exposure history have been exquisitely tracked for over 20 years.
-    Investigation of the association between pre- and postnatal lead levels and criminal activities, diagnosis of Substance Abuse Disorder (SAD), and diagnosis of Antisocial Personality Disorder (ASPD).
- Employ path analysis procedures to determine if academic performance (reading scores and grades) and executive functioning partially mediate the relationship between early lead exposure and adult antisocial behavior.
- Significant relationships were found between indices of early lead exposure and official contacts with the police and judicial system that were evident after covariate adjustment.

**PROJECT 3. “A COMMUNITY-BASED RESEARCH PROJECT "IDENTIFYING RESIDENTIAL HAZARDS USING HOME TEST KITS" **
**Purpose: **to test and validate tools for community members to assess levels of contaminants in their home environment.
-    An evaluation of the effectiveness of “Home Test Kits” for identifying lead and pesticide hazards in the home using a cross-sectional, stratified study design.
-    Healthy Homes Resource Center established at the Cincinnati Better Housing League in Dec. 2002 to create awareness of indoor environmental hazards, provide information, and increase access.
- Partnership with the Better Housing League in Cincinnati and nationally with the Alliance to End Childhood Lead Poisoning and the National Center for Healthy Housing.

-   Enrollment for the HOME study began in February 2003 and is expected to be completed by summer 2005. Samples from the first 50 participants have been analyzed. Lead and injury hazard control interventions are continuing.
-   Methodology for meconium analysis of ethanol metabolites has been successfully transferred to the CDC. Dry weight was determined to be the best denominator of comparison between meconium samples. CDC has developed a GC/MS/MS technique for meconium analysis of ethanol metabolites.
-   A video on the dangers of lead exposure was created and shown as a public service announcement throughout the Cincinnati metropolitan area. The pesticide sampling kit was developed and evaluated. Recruitment began, subjects were accepted into the study, and resident and technician sampling was started (n=15).
-   Recruitment for Project 4 is proceeding (n=127). Analysis of the official record data has been completed for the entire sample.
-   Recruitment for Project 5 is continuing (n=101).
-   Children with both prenatal smoke exposure and the DAT +/+ genotype had significantly elevated hyperactive-impulsive scores compared with children with no smoke exposure and DAT +/- or -/-15.
-   Using data from the National Health and Nutrition Examination Survey (NHANES III), a significant inverse relationship between serum cotinine and scores on reading, math, and block design but not digit span was found that indicate that ETS exposure is associated with cognitive deficits among children aged 6-16 years even at extremely low levels of exposure16.