Effect of Chelation Therapy on the Neuropsychological and Behavioral Development of Lead-Exposed Children After School Entry
* University of Cincinnati College of Medicine, Department of Environmental Health, Cincinnati, Ohio
Harvard University, School of Public Health, Boston, Massachusetts
Children's Hospital of Philadelphia, Department of Psychology, Philadelphia, Pennsylvania
|| National Institute of Environmental Health Sciences, Epidemiology Branch, Research Triangle Park, North Carolina
¶ University of Medicine and Dentistry of New Jersey, Environmental and Occupational Health Sciences Institute, Piscataway, New Jersey #Kennedy Krieger Institute, Baltimore, Maryland
** Children's Hospital of Philadelphia, Department of Adolescent Medicine, Philadelphia, Pennsylvania
University of Medicine and Dentistry of New Jersey, Department of Pediatrics, Newark, New Jersey
Centers for Disease Control and Prevention, Nutritional Biochemistry Branch, Atlanta, Georgia
Objective. Some children in the United States continue to be exposed to levels of lead that increase their risk for lowered intellectual functioning and behavior problems. It is unclear whether chelation therapy can prevent or reverse the neurodevelopmental sequelae of lead toxicity. The objective of this study was to determine whether chelation therapy with succimer (dimercaptosuccinic acid) in children with referral blood lead levels between 20 and 44 µg/dL (0.96-2.12 µmol/L) at 12 to 33 months of age has neurodevelopmental benefits at age 7 years.
Methods. The Treatment of Lead-Exposed Children (TLC) study is a randomized, double-blind, placebo-controlled trial that was conducted between September 1994 and June 2003 in Philadelphia, PA; Newark, NJ; Cincinnati, OH; and Baltimore, MD. Of 1854 referred children who were between the ages of 12 to 33 months and screened for eligibility, 780 were randomized to the active drug and placebo groups stratified by clinical center, body surface area, blood lead level, and language spoken at home. At 7 years of age, 647 subjects remained in the study. Participants were randomly assigned to receive oral succimer or placebo. Up to 3 26-day courses of succimer or placebo therapy were administered depending on response to treatment in those who were given active drug. Eighty-nine percent had finished treatment by 6 months, with all children finishing by 13 months after randomization. All participants received residential lead hazard control measures before treatment. TLC subjects also received a daily multivitamin supplement before and after treatment(s) with succimer or placebo. Scores on standardized neuropsychological measures that tap cognition, behavior, learning and memory, attention, and neuromotor skills were measured.
Results. Chelation therapy with succimer lowered average blood lead levels for 
6 months but resulted in no benefit in cognitive, behavioral, and neuromotor endpoints.
Conclusion. These new follow-up data confirm our previous finding that the TLC regimen of chelation therapy is not associated with neurodevelopmental benefits in children with blood lead levels between 20 and 44 µg/dL (0.96–2.17 µmol/L). These results emphasize the importance of taking environmental measures to prevent exposure to lead. Chelation therapy with succimer cannot be recommended for children with blood lead levels between 20 and 44 µg/dL (0.96–2.12 µmol/L).
Key Words: child • lead • environmental exposure • chelation therapy • succimer • cognition • clinical trials
Abbreviations: CDC, Centers for Disease Control and Prevention • TLC, Treatment of Lead-Exposed Children • NEPSY, Developmental Neuropsychological Assessment • CI, confidence interval
Received for publication Aug 8, 2003; Accepted Nov 4, 2003.
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