Children's Environmental Health Center

Children's Hospital Medical Center

Children's Environmental Health Center
Bruce Lanphear, Ph.D.
bruce.lanphear@chmcc.org
http://www.cincinnatichildrens.org/research/project/enviro/default.htm

Project Description

Exposure to numerous environmental agents, including lead, mercury, PCBs, and environmental tobacco smoke, has been linked with adverse neurobehavioral effects. Still, the ideal biomarker for measuring in utero exposure to specific toxicants has not been established and the adverse effects of many potential neurotoxicants have not been rigorously tested. Fetal exposure is typically measured with self-reported surveys, maternal blood and urine, or cord blood. In contrast, meconium as a biomarker is a non-invasive method to simultaneously test for cumulative exposures to numerous toxicants. But it is unclear whether conventional biomarkers or meconium levels are more predictive of the adverse effects linked with specific toxicants. For lead exposure, emerging data indicate that our efforts should emphasize primary prevention, but the efficacy of lead hazard controls is uncertain, especially for children with low blood lead concentrations. The investigators conducted a cohort study of children, followed from less than 16 weeks gestation to 36 months of age, to examine the effect of low-level exposures to prevalent neurotoxicants. Endpoints include behavioral problems, such as conduct disorder and features consistent with ADHD, cognitive deficits, and hearing loss. The investigators also conducted a nested, randomized, controlled trial to test the efficacy of lead hazard controls on the development of adverse neurobehavioral effects. They tested the following hypotheses: 1) Children in the Lead Reduction Group will have blood lead levels that are 2.7 ug/dL (30%) or lower, significantly higher cognitive scores, less hearing loss, and fewer behavioral problems than one Control group at 36 months of age. 2) Fetal and postnatal exposures to pesticides, ETS and lead (at blood levels below 10 ug/dL) are associated with adverse neurobehavioral effects, growth delay and hearing loss in early childhood. 3) Fetal exposures, as measured by survey (ETS), maternal and cord blood (lead, methyl mercury, pesticides and ETS), and urine (pesticides), are less predictive of the adverse effects of toxicants on cognition, behavioral problems and hearing, compared with the same toxicants in meconium. This project, in combination with the research described in Project 2, tests the efficacy of an intervention for the primary prevention of lead toxicity, as measured by lead concentration and neurobehavioral functioning at 36 months of age, serve as a model to evaluate the adverse effects of exposures to multiple prevalent toxicants among fetuses and children test meconium levels as a biomarker of fetal exposure to numerous toxicants, and provides exposure and risk assessment data for residential pesticides.

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Project Highlights

One of the Center's achievements is research implicating lead and prenatal tobacco exposure as antecedents for ADHD in children.  Center investigators have, for example, conducted studies linking gene-environment interactions - dopamine-associated polymorphisms, DAT1 and DRD4 with lead and tobacco exposure - with ADHD in children. These studies indicate that children with high-risk dopamine-associated polymorphisms are more susceptible to lead and tobacco exposure.  Males were at particular risk for lead-associated executive dysfunction.  Center investigators also found that childhood lead exposure and prenatal tobacco exposure are risk factors for doctor-diagnosed ADHD, accounting for about 1 out of 3 cases of ADHD in U.S. children. 

• Kahn RS, Khoury JC, Nichols WC, Lanphear BP. Role of dopamine transporter genotype and maternal prenatal smoking in childhood hyperactivity-impulsivity, inattentive and oppositional behaviors. Journal of Pediatrics 2003:143: 104-110.
• Braun J, Kahn RS, Froehlich T, Auinger P, Lanphear BP.  Exposures to environmental toxicants and attention deficit hyperactivity disorder in U.S. children.  Environ Health Perspectives 2006 (in press).   
• Froehlich T, Lanphear BP, Dietrich KN, Cory-Slechta D, Wang N, Kahn RS.  ADHD-related Executive Function:  Interactions of the DRD4 Polymorphism, Lead, and Sex.  Biologic Research 2006 (in press). 

The Center has been at the forefront of research implicating low-level exposure to environmental toxicants on intellectual and behavioral functions of children, including lead exposure at blood lead levels below 10 mg/dL and ETS exposure.  These studies have led national and international agencies to re-examine the action levels set for lead exposure and raised questions about adverse consequences of low-level exposure to a variety of environmental chemicals.    

1. Canfield RL, Henderson CR, Cory-Slechta DA, Cox C, Jusko TA, Lanphear BP. Intellectual impairment in children with blood lead concentrations below 10 micrograms per deciliter. N Engl J Med 2003;348:1517-1526. 
2. Lanphear BP, Hornung R, Khoury J, Yolton K, Baghurst P, Bellinger DC, Canfield RL, Dietrich KN, Bornschein R, Greene T, Rothenberg SJ, Needleman HL, Schnaas L, Wasserman G, Graziano J.  Low-level environmental lead exposure and children’s intellectual function: An international pooled analysis.  Environ Health Perspect 2005;113:894-899.
3. Yolton K (New Scientist), Auinger P, Dietrich KN, Lanphear BP, Hornung R. Exposure to environmental tobacco smoke and cognitive abilities in US children and adolescents. Environ Health Persp 2005:113:98-103. 
4. Braun J, Kahn RS, Froehlich T, Auinger P, Lanphear BP.  Exposures to environmental toxicants and attention deficit hyperactivity disorder in U.S. children.  Environ Health Perspectives 2006 (in press).  

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