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The effect of chelation therapy with succimer on neuropsychological development in children exposed to lead
W J Rogan1, K N Dietrich, J H Ware
1National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. rogan@niehs.nih.gov
Insights
Succimer treatment lowered blood lead levels in children but did not improve cognitive or behavioral outcomes. Chelation therapy is not recommended for children with blood lead levels below 45 microg/dL.
Area of Science:
- Environmental Health
- Pediatric Toxicology
- Clinical Trials
Background:
- Childhood lead exposure from urban housing causes cognitive impairment.
- The efficacy of treatments to reduce blood lead levels in preventing impairment is unknown.
Purpose of the Study:
- To evaluate the effectiveness of succimer in reducing blood lead levels and improving neurodevelopmental outcomes in young children.
- To determine if lead chelation therapy is beneficial for children with elevated blood lead levels.
Main Methods:
- A randomized, placebo-controlled, double-blind trial involving 780 children aged 12-33 months with blood lead levels of 20-44 microg/dL.
- Children received up to three courses of oral succimer or placebo.
- Neuropsychological, cognitive, motor, and behavioral function were assessed over 36 months.
Main Results:
- Succimer significantly reduced blood lead levels compared to placebo in the first six months.
- No statistically significant differences were observed in IQ scores, behavior, or neuropsychological assessments at 36 months.
- Observed differences in outcomes were small, with some measures showing slight non-significant improvements or worsening in the succimer group.
Conclusions:
- Succimer effectively lowers blood lead levels in children but does not improve cognitive, behavioral, or neuropsychological function.
- Chelation therapy with succimer is not indicated for children with blood lead levels below 45 microg/dL.
- Current lead chelators, including succimer, are not beneficial for this population.
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.
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