Toxicity Of Lead In Children--clinical Trial

Environmental Health Sciences

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Abstract

Prospective data from multiple studies in several countries show that lead exposure insufficient to produce symptoms still results in cognitive deficits in young children. Peak blood lead level, which is usually achieved around two years of age, is associated with lower scores on IQ tests administered at age 4 years and later. It is not known whether such effects can be reduced or prevented once exposure has taken place. To answer this question, we designed and supported the Treatment of Lead-exposed Children Trial (TLC), which was a 780 child, randomized trial in which children were given succimer, a drug that lowers blood lead level quickly, or placebo, and then followed for three years until they were about 5 years old. In a paper published in May, 2001, we reported that treating the children with succimer lowered their lead levels but did not produce better scores on tests designed to test cognitive, behavioral, and neuropsychological function. We are following the children until they are 7 years old, however, to see if a difference in function emerges during the very challenging period when they enter school. This year we did a different analysis of the data from the TLC trial, examining whether children whose blood lead levels fell the most had improved test scores,whether or not they had been given a drug to lower their blood lead levels. We did this because there was an observational study in which New York children 13-87 months old with blood lead levels between 25 and 55 mg/dL were given chelation when clinically indicated, then followed for 6 months. Those whose blood lead levels fell the most had improved cognitive test scores, independent of whether they had been given iron or chelation therapy. By 6 months after randomization, blood lead levels had fallen by similar amounts in both chelated and placebo children, despite the immediate drops in the chelated group; there was no association between change in blood lead level and change in cognitive test score. Blood lead levels continued to fall. At 36 months follow-up, in the placebo group only, cognitive test scores had increased 4.0 points per 10 ug/dL fall in blood lead level from baseline to 36 months follow-up (p < 0.01) and 5.1 points (p < 0.01) from six to 36 months. The improvement in scores in the placebo group only implies that factors other than declining blood lead levels per se are responsible for cognitive improvement; it is possible but less likely that succimer, the active drug, impairs cognition.