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OBJECTIVES. The purpose of this work was to assess the long-term impact of childhood lead exposure on the neurosubstrate of language function and brain organization. METHODS. Young adults from the Cincinnati Lead Study were recruited to undergo functional magnetic resonance image scanning while performing a verb generation task. These subjects have been followed from birth through early childhood with extensive documentation of lead exposure, neuropsychology, and behavior. Forty-two subjects provided useful imaging data. The locale, strength, and the correlation between brain language activation and childhood blood lead concentration were studied. RESULTS. After adjusting for potential confounders, the activation in left frontal cortex, adjacent to Broca's area, and left middle temporal gyrus, including Wernicke's area, were found to be significantly associated with diminished activation in subjects with higher mean childhood blood lead levels, whereas the compensatory activation in the right hemisphere homolog of Wernicke's area was enhanced in subjects with higher blood lead levels. CONCLUSION. This study indicates that childhood lead exposure has a significant and persistent impact on brain reorganization associated with language function. www.pediatrics.org/cgi/doi/10.1542/ peds.2006-0467 doi:10.1542/peds.2006-0467 Key Words environmental pollutants, lead poisoning, neuroimaging, language development, pediatric research Abbreviations fMRI--functional magnetic resonance imaging CLS--Cincinnati Lead Study EPI--echo planar imaging BOLD--blood oxygen level dependant SES--socioeconomic status IQ--intelligence quotient ROI--region of interest, CHILDHOOD LEAD EXPOSURE is inversely associated with intellectual abilities, academic achievement, and psychomotor development. (1-4) Even low-level lead exposure can negatively impact a wide range of cognitive functions, such as [...]

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 [...]

Objective. Exposure to lead at levels encountered by urban children impairs cognitive development. An observational study suggested improvement in IQ when blood lead level fell, but the only randomized trial of chelation showed no benefit in IQ. Methods. We did a new analysis of the data from the clinical trial using change in blood lead level as the independent variable. The 741 children began with blood lead levels between 20 and 44 [micro]g/dL, and were 13 to 33 months old at randomization to chelation or placebo. Blood lead levels were measured repeatedly, and cognitive tests were given at baseline, 6 months, and 36 months follow-up. Results. 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 [micro]g/dL fall in blood lead level from baseline to 36 months follow-up and 5.1 points from 6 to 36 months. Conclusions. 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. Pediatrics 2002;110: 787-791; child, preschool; environmental exposure; lead poisoning/blood/etiology; cognition/physiology; chelation therapy., ABBREVIATIONS. TLC, Treatment of Lead-Exposed Children; MDI, Mental Development Index; SD, standard deviation. Prospective data from multiple studies in several countries show that lead exposure insufficient to produce symptoms still [...]

Children exposed to low to moderate levels of lead may have a higher risk of impaired motor development than those who are not. Lead affects the central nervous system and can impair mental development in children. A study examined the effect of exposure to low to moderate levels of lead on the neuromotor skills of 245 six-year-old children from the inner city. Children with increased blood levels of lead as newborns were more likely to suffer from reduced dexterity, visual-motor control and upper-limb speed than those with lower blood levels. Increased blood levels of lead during infancy were also associated with reduced bilateral and fine-motor coordination. Balance and response speed were not affected by exposure to low or moderate levels of lead. Prenatal exposure to low or moderate levels of lead was not associated with impaired motor development., The relationship between asymptomatic lead exposure and subtle deficits in intellectual attainment has been relatively well established by modern studies. However, neuromotor performance has rarely been the focus of these investigations. It was postulated that motor developmental outcomes may be more sensitive indicators of lead's adverse effects on the central nervous system as they are probably less confounded with social factors than cognitive and academic outcomes. A comprehensive neuromotor assessment battery was administered to 245 six-year-old urban inner-city children enrolled in the Cincinnati Lead Study. These children have been followed since birth with quarterly assessments of blood lead concentrations, medical status, and neurobehavioral development. Prior to covariate adjustment, neonatal, but not prenatal blood lead levels were associated with poorer scores on assessments of bilateral coordination, upper-limb speed and dexterity, and a composite index of fine-motor coordination. Averaged postnatal blood lead levels were also associated with lower scores on the aforementioned subtests as well as a measure of visual-motor control. Following statistical adjustment for covariates, neonatal blood lead levels were associated with poorer performance on a measure of upper-limb speed and dexterity and the fine-motor composite. Postnatal blood lead levels remained significantly associated with poorer scores on measures of bilateral coordination, visual-motor control, upper-limb speed and dexterity, and the fine-motor composite. Low to moderate lead exposure is associated with moderate deficits in gross and especially fine-motor developmental status. Results of this study provide support for recent initiatives to reduce the exposure of children to sources of environmental lead. Pediatrics 1993;91:301-307, lead, motor development, toxicology, environmental health.

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.)

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.)

BACKGROUND. Lead exposure in childhood lowers IQ scores, but its effect on children's behavior is less clear. Because IQ, per se, affects behavior, measuring the direct effect of lead requires [...]

Abstract. A prospective method was used in this study to assess the effects of fetal lead exposure on neurodevelopmental status in 3- and 6-month old infants. At their first prenatal medical appointments, 305 lower socioeconomic status women residing in predesignated lead-hazardous areas of Cincinnati were recruited. Lead was measured in whole blood in both the mother and fetal-placental unit (prenatal and cord) and the neonate (ten days and 3 months). All blood lead levels were less than 30 micro g/dL. Infant development was assessed with the Bayley scales at 3 and 6 months of age. Multiple regression analyses which treated perinatal health factors such as birth weight and gestation as confounders indicated an independent, inverse relationship between both prenatal and neonatal blood lead levels and performance on the Bayley Mental Developmental Index at both ages. Male infants and infants from the poorest families appeared to be especially sensitive to these psychoteratogenic influences. Further study using a structural equations approach indicated that neurobehavioral deficits were partly mediated by lead-related reductions in birth weight and gestation. [ABSTRACT FROM AUTHOR]

Abstract. The social and developmental correlates of early lead exposure were explored in an interim analysis of data from an ongoing longitudinal investigation in Cincinnati. Regardless of the apparent net availability of lead in the infant's physical environment, parental behavior was still significantly associated with infant blood lead levels. However, this was only the case after infants in the study reached 6 months of age and beyond when prewalking progression and early walking made parental management all the more critical. Future lead screening and abatement programs should include supports for the caretaker-child relationship. Pediatrics 1985;75:1114-1119; lead exposure, child development, caretaker-child interaction. [ABSTRACT FROM AUTHOR]

Abstract. A total of 53 mother-infant dyads, divided into five diagnostic groups (nonaccidental trauma combined with failure-to-thrive, nonaccidental trauma combined with iron-deficiency anemia, nonaccidental trauma only, neglect only, and normal control subjects) were observed during a feeding session. Qualitative differences were found in the relational characteristics of dyads in which multiple forms of maltreatment existed. Developmental examinations revealed that infants subjected to severe abuse and neglect were significantly retarded in their mental and motor development compared with the remaining index and control groups. The results were interpreted to suggest that relational disturbances are at the core of the problem of infant maltreatment and that on the basis of interactional symptomatology, two broadly different clinical conditions have been identified. [ABSTRACT FROM AUTHOR]