Source:Rogan WJ, Dietrich KN, Ware JH, et al, for the Treatment of Lead-Exposed Children Trial Group. The effect of chelation therapy with succimer on neuropsychological development in children exposed to lead.
N Engl J Med.

Elevated lead levels are still a common problem in general pediatrics. Standard practice to date has been to consider chelation therapy for children whose lead levels exceed 20mcg/dL and to treat those with levels exceeding 45 mcg/dL. The efficacy of this practice on long-term cognitive outcomes has not been well assessed. In this large randomized, placebo-controlled, double-blind trial, the authors investigated whether children with moderately high blood lead levels (20–44mcg/dL) benefit from oral chelation with succimer as measured by improved scores on a range of tests measuring cognition, neuropsychological function, and behavior. Seven hundred eighty children aged 12–33 months with 2 blood lead levels of 20–44 mcg/dL were randomized to succimer (1050mg per square meter of body-surface area per day for the first 7 days and 700mg per square meter of body-surface area for days 8–26) or placebo. They received up to 2 additional courses of treatment if their lead levels remained above 15mcg/dL 2 weeks after a course of treatment. The Bayley Scale of Infant Development II was administered to all children at baseline, and outcomes were assessed at 18 months using the Bayley or the Wechsler Preschool and Primary Scales of Intelligence-Revised, depending on the age of the child. Outcomes at 36 months were assessed using the Wechsler, the Developmental Neuropsychological Assessment, and the Conners’ Parent Rating Scale.

The average age of the study participants was 24 months, and the average blood lead level was 26 mcg/dL. The scores on the various scales were nearly identical for the treatment and placebo groups at baseline, 18 months, and 36 months, and none reached statistical significance. Blood lead levels dropped faster in the succimer group, but rebounded within 1 week of each treatment course. Blood lead levels also dropped steadily in the placebo group. At the end of 1 year, blood lead levels were 2.7 mcg/dL lower in the treatment group than in the placebo group. This difference was statistically significant. Ten children in the succimer group and 7 in the placebo group had blood lead levels that exceeded 44 mcg/dL. Of these, 9 in the treatment group and 4 in the placebo group required hospitalization for chelation. Children in the succimer group grew on average .35 cm less than children in the placebo group over 34 months of follow-up, and 5 children in the succimer group and none in the placebo group were hospitalized for trauma. Decreased growth is not a recognized side effect of succimer. The authors continue to follow these children, and plan a follow-up analysis at 7 years of age. They conclude that unless a more positive outcome is apparent at that time, drug therapy should be used with caution in this group.

This study lays the groundwork for better-informed decisions about...

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