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Objective. Some children in the United States continue to be exposed to levels of lead that increase their risk for lowered intellectual functioning and behavior problems. It is unclear whether chelation therapy can prevent or reverse the neurodevelopmental sequelae of lead toxicity. The objective of this study was to determine whether chelation therapy with succimer (dimercaptosuccinic acid) in children with referral blood lead levels between 20 and 44 [micro]g/dL (0.96-2.12 [micro]mol/L) at 12 to 33 months of age has neurodevelopmental benefits at age 7 years. Methods. The Treatment of Lead-Exposed Children (TLC) study is a randomized, double-blind, placebo-controlled trial that was conducted between September 1994 and June 2003 in Philadelphia, PA; Newark, NJ; Cincinnati, OH; and Baltimore, MD. Of 1854 referred children who were between the ages of 12 to 33 months and screened for eligibility, 780 were randomized to the active drug and placebo groups stratified by clinical center, body surface area, blood lead level, and language spoken at home. At 7 years of age, 647 subjects remained in the study. Participants were randomly assigned to receive oral succimer or placebo. Up to 3 26-day courses of succimer or placebo therapy were administered depending on response to treatment in those who were given active drug. Eighty-nine percent had finished treatment by 6 months, with all children finishing by 13 months after randomization. All participants received residential lead hazard control measures before treatment. TLC subjects also received a daily multivitamin supplement before and after treatment(s) with succimer or placebo. Scores on standardized neuropsychological measures that tap cognition, behavior, learning and memory, attention, and neuromotor skills were measured. Results. Chelation therapy with succimer lowered average blood lead levels for ~6 months but resulted in no benefit in cognitive, behavioral, and neuromotor endpoints. Conclusion. These new follow-up data confirm our previous finding that the TLC regimen of chelation therapy is not associated with neurodevelopmental benefits in children with blood lead levels between 20 and 44 [micro]g/dL (0.96-2.17 [micro]mol/L). These results emphasize the importance of taking environmental measures to prevent exposure to lead. Chelation therapy with succimer cannot be recommended for children with blood lead levels between 20 and 44 [micro]g/dL (0.96-2.12 [micro]mol/L). Pediatrics 2004;114:19-26; child, lead, environmental exposure, chelation therapy, succimer, cognition, clinical trials. ABBREVIATIONS. CDC, Centers for Disease Control and Prevention; TLC, Treatment of Lead-Exposed Children; NEPSY, Developmental Neuropsychological Assessment; CI, confidence interval., Before the availability of chelating drugs, as many as 45% of lead-poisoned children who presented with signs or symptoms of encephalopathy died, and more than one quarter of surviving patients [...]

Exposure to lead, as with other heavy metals, is detrimental to a variety of body systems. In addition, infant growth may be affected. Previous research has suggested that infants exposed to lead both prenatally and during infancy had poorer growth rates through the fifteenth month of life. To extend this research, the same group of infants were studied through 33 months of age. Of 260 infants originally studied, 235 children were still available for follow-up. Their heights were assessed to determine if both prenatal and postnatal lead exposure continued to influence growth rate. The actual height of the children at 33 months correlated significantly with height at 18 months. Blood lead concentration (PbB) correlated weakly with growth and height at 33 months in a way that suggested that early postnatal lead exposure was important. Thus, prenatal lead exposure did not directly predict height at 33 months, while lead exposure from 3 to 15 months after birth influenced stature and was related to lead exposure during the second and third years of life. Blood lead levels of 20 to 25 micrograms per deciliter were considered as possibly borderline for association with growth retardation. Surprisingly, children who were exposed to only low lead levels at 18 to 33 months of age and were previously exposed to high levels were taller than children who were exposed only to low lead levels, and this was attributed to a catch-up phenomenon occurring between 18 and 33 months. Children's stature was also significantly affected by their iron status and by maternal smoking. The report suggests that prenatal and early postnatal effects of lead on stature may be compensated for during a subsequent catch-up period if lead exposure is minimal during that period. (Consumer Summary produced by Reliance Medical Information, Inc.)

Lead exposure, even at low levels, can have toxic effects in several organ systems. Previous studies have indicated that exposure to lead can adversely affect vitamin D metabolism. Vitamin D metabolites are important for maintaining the body's balance of calcium and phosphorus. Bone is the primary site of lead accumulation, but the effects of lead exposure on bone mineralization are not known. Therefore, the effect of chronic low-to-moderate lead exposure on vitamin D metabolism and bone mineralization was assessed in 105 children who had been exposed to lead since birth. These children had an adequate intake of calcium phosphorus and vitamin D. The subjects were studied at either 21, 27, or 33 months of age. No relationship between blood levels of lead and vitamin D metabolites or bone mineral content was found. The findings suggest that children with adequate nutrition (containing sufficient levels of vitamin D, calcium, and phosphorus), after low-to-medium levels of lead exposure, do not have significant alterations in vitamin D metabolism; there were also no effects of lead on bone mineralization observed. (Consumer Summary produced by Reliance Medical Information, Inc.)

Stunted growth in children has long been associated with lead exposure. In recent years, exposure to lead has been found to interfere specifically with the attainment of normal stature (height). This aspect of asymptomatic lead exposure in children was examined in 260 infants who were followed from birth to age 15 months. The study subjects were from an area with a high incidence of lead poisoning. Lead levels in the body were assessed by measuring blood concentrations at three-month intervals. In addition, fetal lead exposure was determined by measuring the lead concentrations in the mothers' blood during pregnancy. It was found that high lead concentrations in the pregnant mothers were linked to high lead concentrations in the infants, and this had a detrimental effect upon the infants' growth. In general, children of mothers with higher prenatal blood lead concentrations had average growth that was approximately 2 centimeters (1 inch) less than normal stature at 15 months, if the infants continued to be exposed to lead from 3 to 15 months of age. It was also found that if lead exposure was avoided after birth, poor growth outcome would not necessarily follow prenatal lead exposure. The mechanism by which lead exposure influences growth is still unclear, and the duration of the effects of early exposure is not known. (Consumer Summary produced by Reliance Medical Information, Inc.)

In this article we describe the assessment and control of lead dust exposure in the Treatment of Lead-exposed Children (TLC) Trial, a clinical trial of the effects of oral chelation on developmental end points in urban children with moderately elevated blood lead levels. To reduce potential lead exposure from settled dust or deteriorated paint during the drug treatment phase of the trial, the homes of 765 (98%) of the randomized children (both active and placebo drug treatment groups) were professionally cleaned. Lead dust measurements were made in a sample of 213 homes before and after cleaning. Geometric mean dust lead loadings before cleaning were 43, 29, 308, and 707 micro g/ft2 in the kitchen floor, playroom floor, playroom windowsill, and playroom window well samples respectively. Following cleaning, floor dust lead loadings were reduced on average 32% for paired floor samples (p < 0.0001), 66% for windowsills (p < 0.0001), and 93% for window wells (p < 0.0001). Cleaning was most effective for 146 homes with precleaning dust lead levels above the recommended clearance levels, with average reductions of 44%, 74%, and 93% for floors (p < 0.0001), windowsills (p < 0.0001), and window wells (p < 0.0001), respectively. Despite these substantial reductions in dust lead loadings, a single professional cleaning did not reduce the lead loadings of all dust samples to levels below current federal standards for lead in residential dust. Attainment of dust levels below current standards will require more intensive cleaning and lead hazard reduction strategies.