The effect of chelation therapy with succimer on neuropsychological development in children exposed to lead

N Engl J Med. 2001 May 10;344(19):1421-6. doi: 10.1056/NEJM200105103441902.


Background: Thousands of children, especially poor children living in deteriorated urban housing, are exposed to enough lead to produce cognitive impairment. It is not known whether treatment to reduce blood lead levels prevents or reduces such impairment.

Methods: We enrolled 780 children with blood lead levels of 20 to 44 microg per deciliter (1.0 to 2.1 micromol per liter) in a randomized, placebo-controlled, double-blind trial of up to three 26-day courses of treatment with succimer, a lead chelator that is administered orally. The children lived in deteriorating inner-city housing and were 12 to 33 months of age at enrollment; 77 percent were black, and 5 percent were Hispanic. Follow-up included tests of cognitive, motor, behavioral, and neuropsychological function over a period of 36 months.

Results: During the first six months of the trial, the mean blood lead level in the children given succimer was 4.5 microg per deciliter (0.2 micromol per liter) lower than the mean level in the children given placebo (95 percent confidence interval, 3.7 to 5.3 microg per deciliter [0.2 to 0.3 micromol per liter]). At 36 months of follow-up, the mean IQ score of children given succimer was 1 point lower than that of children given placebo, and the behavior of children given succimer was slightly worse as rated by a parent. However, the children given succimer scored slightly better on the Developmental Neuropsychological Assessment, a battery of tests designed to measure neuropsychological deficits thought to interfere with learning. All these differences were small, and none were statistically significant.

Conclusions: Treatment with succimer lowered blood lead levels but did not improve scores on tests of cognition, behavior, or neuropsychological function in children with blood lead levels below 45 microg per deciliter. Since succimer is as effective as any lead chelator currently available, chelation therapy is not indicated for children with these blood lead levels.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Chelating Agents / therapeutic use*
  • Chelation Therapy*
  • Child Behavior / drug effects*
  • Child Development / drug effects*
  • Child, Preschool
  • Cognition / drug effects
  • Double-Blind Method
  • Female
  • Humans
  • Infant
  • Intelligence / drug effects*
  • Lead / blood
  • Lead Poisoning / drug therapy*
  • Male
  • Neuropsychological Tests
  • Poverty Areas
  • Succimer / therapeutic use*
  • Urban Population


  • Chelating Agents
  • Lead
  • Succimer