Project 1: Neurobehavioral Effects of Prevalent Toxicants in Children
Investigator: Bruce P. Lanphear, MD, MPH
Project Period: 10-1-2001 through 6-30-2006
Objectives / Hypothesis
Epidemiologic and experimental data have established the adverse effects of numerous environmental toxicants, including lead, alcohol, mercury, PCB’s, and environmental tobacco smoke (ETS) on children’s brain function. In utero exposure to these toxicants has been linked with cognitive deficits and behavioral problems. Lead exposure has been linked to specific behavioral problems, including conduct disorder and delinquency. Exposure to lead has been linked with mental retardation and ADHD-like features. Still, many studies linking environmental toxicants with neurobehavioral effects have only examined children with high exposures. There is emerging evidence that adverse effect of exposure to lead, mercury, and PCB’s occur at levels previously thought to be low. There is also data linking exposures to pesticides with adverse neurobehavioral effects, but the data are too sparse to draw any conclusions.
The ideal biomarkers for measuring in utero exposure to specific toxicants have not been established. Fetal exposure is typically measured with surveys, maternal blood, urine, or hair. Meconium, a longer-term measure of in utero exposure, has only been validated as a measure of cocaine and ETS exposure, but it offers numerous advantages. It is a non-invasive method that may be useful to simultaneously test for exposure to numerous toxicants. Still, it is unclear whether conventional biomarkers or meconium is more predictive of the adverse effects associated with specific toxicants. For lead exposure, emerging data indicate that we should emphasize primary prevention, but the safety and efficacy of lead hazard controls are uncertain, especially for children with lower blood lead concentrations. We will test the following hypotheses:
- In utero exposures measured by survey (alcohol and ETS), maternal and cord blood (lead and mercury), maternal and cord serum (ETS), and urine (pesticides) are less predictive of in utero effects of prevalent toxicants, including cognition, behavior problems, and growth and hearing compared with the same toxicants in meconium.
- Prenatal and postnatal exposures to prevalent pesticides and ETS are associated with adverse neurobehavioral effects, growth delay, and hearing loss in children.
- Children in the Lead Hazard Reduction Group will have blood lead concentration that are 2.7 mg / dL (30%) or lower at 36 months of age, significantly higher cognitive scores, less hearing loss, greater growth velocity, and fewer behavioral problems and developmental disorders compared with those in the Control Group.
Approach
We propose to conduct a longitudinal cohort study to examine the dose-response of low-level exposures (pre and postnatal) to prevalent neurotoxins with neurobehavioral outcomes and specific development conditions, including conduct disorder and behaviors consistent with ADHD. We will also conduct a nested, randomized, controlled trial to test the efficacy of lead hazard controls on blood lead concentrations.
Expected Results
This proposed trial would be the first to attempt to validate meconium as a measure of exposure to numerous neurotoxicants and to test the efficacy of a lead hazard control on blood lead concentration and neurobehavioral functioning. This cohort study will simultaneously evaluate the adverse effects of exposures to multiple prevalent toxicants in the human population during early childhood and validate the use of meconium as a measure of in utero exposures to multiple environmental neurotoxins.
