A Study of the Health Effects of Childrens Exposure to Prevalent Neurotoxicants in an Urban Communit

1
A Study of the Health Effects of Childrens
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
Childrens Environmental Health, Cincinnati
Childrens Hospital.

• 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.

Future Directions
Results/Conclusions
Methods/Approach
Science Question
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.

• 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
  (n15).
• Recruitment for Project 4 is proceeding
  (n127). Analysis of the official record data has
  been completed for the entire sample.
• Recruitment for Project 5 is continuing
  (n101).
• 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.

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
Childrens Environmental Health Center (CCEHC) at
the Cincinnati Childrens Medical Center is
conducting ORD-sponsored research through a
Science-To-Achieve-Results (STAR) Program center
grant to address the links between childrens
exposure to chemicals and adverse neurobehavioral
effects1.

• 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.

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 871-95 Jacobsen JL, et. al.
  New England Journal of Medicine 1996 335783-9.
• 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. 200010(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-impulsiv
  e, 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?

• 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.

Research Goals

• 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.

• 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 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.

Impact and Outcomes
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.