The Effect of Chelation Therapy with Succimer on Neuropsychological Development in Children Exposed to Lead
Walter J. Rogan, M.D., Kim N. Dietrich, Ph.D., James H. Ware, Ph.D., Douglas W. Dockery, Ph.D., Mikhail Salganik, Ph.D., Jerilynn Radcliffe, Ph.D., Robert L. Jones, Ph.D., N. Beth Ragan, B.A., J. Julian Chisolm, M.D., George G. Rhoads, M.D., for the Treatment of Lead-Exposed Children Trial Group
Background Thousands of children, especially poor children livingin deteriorated urban housing, are exposed to enough lead toproduce cognitive impairment. It is not known whether treatmentto reduce blood lead levels prevents or reduces such impairment.
Methods We enrolled 780 children with blood lead levels of 20to 44 µg per deciliter (1.0 to 2.1 µmol per liter)in a randomized, placebo-controlled, double-blind trial of upto three 26-day courses of treatment with succimer, a lead chelatorthat is administered orally. The children lived in deterioratinginner-city housing and were 12 to 33 months of age at enrollment;77 percent were black, and 5 percent were Hispanic. Follow-upincluded tests of cognitive, motor, behavioral, and neuropsychologicalfunction over a period of 36 months.
Results During the first six months of the trial, the mean bloodlead level in the children given succimer was 4.5 µg perdeciliter (0.2 µmol per liter) lower than the mean levelin the children given placebo (95 percent confidence interval,3.7 to 5.3 µg per deciliter [0.2 to 0.3 µmol perliter]). At 36 months of follow-up, the mean IQ score of childrengiven succimer was 1 point lower than that of children givenplacebo, and the behavior of children given succimer was slightlyworse as rated by a parent. However, the children given succimerscored slightly better on the Developmental NeuropsychologicalAssessment, a battery of tests designed to measure neuropsychologicaldeficits thought to interfere with learning. All these differenceswere small, and none were statistically significant.
Conclusions Treatment with succimer lowered blood lead levelsbut did not improve scores on tests of cognition, behavior,or neuropsychological function in children with blood lead levelsbelow 45 µg per deciliter. Since succimer is as effectiveas any lead chelator currently available, chelation therapyis not indicated for children with these blood lead levels.
Source Information
From the National Institute of Environmental Health Sciences, Research Triangle Park, N.C. (W.J.R., N.B.R.); the Department of Environmental Health, University of Cincinnati, Cincinnati (K.N.D.); the Harvard School of Public Health, Boston (J.H.W., D.W.D., M.S.); the Department of Psychology, Children's Hospital of Philadelphia, Philadelphia (J.R.); the Nutritional Biochemistry Branch, Centers for Disease Control and Prevention, Atlanta (R.L.J.); the KennedyKrieger Institute, Baltimore (J.J.C.); and the Environmental and Occupational Health Sciences Institute, University of Medicine and Dentistry of New Jersey, Piscataway (G.G.R.). Presented in part at the National Lead Grantee Conference of the Centers for Disease Control and Prevention, Atlanta, December 11, 2000, and at the Society of Toxicology meeting, San Francisco, March 27, 2001.
Address reprint requests to Dr. Rogan at the Epidemiology Branch, National Institute of Environmental Health Sciences, A3-05, P.O. Box 12233, Research Triangle Park, NC 27709, or at rogan{at}niehs.nih.gov.
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