Early exposure to lead and juvenile delinquency.

Cross-sectional studies have reported an association between lead (Pb) levels in bone and delinquent behavior in later childhood and adolescence. This is the first prospective longitudinal study of Pb and child development to address this question with comprehensive assessments of toxicant exposure and other developmental cofactors. A prospective longitudinal birth cohort of 195 urban, inner-city adolescents recruited between 1979 and 1985 was examined. Relationships between prenatal and postnatal exposure to Pb (serial blood Pb determinations) and antisocial and delinquent behaviors (self- and parental reports) were examined. Prenatal exposure to Pb was significantly associated with a covariate-adjusted increase in the frequency of parent-reported delinquent and antisocial behaviors, while prenatal and postnatal exposure to Pb was significantly associated with a covariate-adjusted increase in frequency of self-reported delinquent and antisocial behaviors, including marijuana use. Use of marijuana itself by Cincinnati Lead Study (CLS) teens was strongly associated with all measures of delinquent and antisocial behavior. This prospective longitudinal study confirmed earlier clinical observations and recent retrospective studies that have linked Pb exposure with antisocial behavior in children and adolescents. Both prenatal and postnatal exposure to Pb were associated with reported antisocial acts and may play a measurable role in the epigenesis of behavioral problems independent of the other social and biomedical cofactors assessed in this study.

The contribution of lead-contaminated house dust and residential soil to children's blood lead levels. A pooled analysis of 12 epidemiologic studies.

In 1992, the U.S. Congress passed the Residential Lead-Based Paint Hazard Reduction Act, which requires the promulgation of health-based dust lead and soil lead standards for residential dwellings to prevent undue lead exposure in children. Unfortunately, the levels of lead in house dust and soil that are associated with elevated blood lead levels among U.S. children remain poorly defined. This pooled analysis was done to estimate the contributions of lead-contaminated house dust and soil to children's blood lead levels. The results of this pooled analysis, the most comprehensive existing epidemiologic analysis of childhood lead exposure, confirm that lead-contaminated house dust is the major source of lead exposure for children. These analyses further demonstrate that a strong relationship between interior dust lead loading and children's blood lead levels persists at dust lead levels considerably below the U.S. Department of Housing and Urban Development's current postabatement standards and the Environmental Protection Agency's guidance levels. Finally, these analyses demonstrate that a child's age, race, mouthing behaviors, and study-site specific factors influence the predicted blood lead level at a given level of exposure. These data can be used to estimate the potential health impact of alternative health-based lead standards for residential sources of lead exposure.

Field testing of new aerosol sampling method with a porous curved surface as inlet.

A new aerosol sampling method, utilizing a porous curved surface as the sampling inlet, has recently been developed. Previous laboratory evaluations of this method have demonstrated its important features, such as low wind sensitivity and good filter collection uniformity. In this study a prototype incorporating the new method was evaluated in the field as a stationary and personal sampling device. The small sampler, utilizing a 25-mm filter is called the button aerosol sampler and was evaluated for collecting total airborne dust and fungal spores. The study was performed in nine poorly maintained inner-city houses during environmental cleanups at different cleanliness levels. The button sampler was used in parallel with the standard 37-mm closed-face filter cassette. Four collocated samplers of each type were tested at all sites as stationary samplers, and three samplers of each type were tested at two sites as personal samplers. Aerosol samples were collected on filters and analyzed using the gravimetric method for total dust and epifluorescence microscopy for fungal spores. The average particle concentration values measured with the button sampler and with the standard sampling cassette were found to correlate well within ranges of 10(1)-10(3) micrograms/m3 for total dust and 10(3)-10(5) spores/m3 for airborne fungi. The measurement results obtained with the new button sampler showed lower intersample variations of the measured concentration levels and higher uniformity of the particle deposits on the filters than those obtained with the standard cassette.

Urinary arsenic excretion as a biomarker of arsenic exposure in children.

Urinary arsenic concentration has been used generally for the determination of exposure, but much concern has been raised over the most appropriate expression for urinary arsenic levels. In this study, we examined the influence of various adjustments of expressing urinary arsenic data. All children who were less than 72 mo of age and who were potty trained were invited to participate in the present study. Urine, soil, and dust samples were collected, and arsenic measurements were made. The geometric mean of speciated urinary arsenic among children who provided first-voided urine samples on 2 consecutive mornings was 8.6 microg/l (geometric standard deviation = 1.7, n = 289). Speciated urinary arsenic was related significantly to soil arsenic in bare areas (p < .0005). Use of a single urine sample versus the average of two first-voided urine samples collected on 2 consecutive mornings did not significantly alter the relationship between environmental arsenic and urinary arsenic levels. Furthermore, none of the adjustments to urinary concentration improved the strength of correlation between urinary arsenic and soil arsenic levels. Concentration adjustments may not be necessary for urinary arsenic levels obtained from young children who provide first-void samples in the morning.

Assessment of reproductive disorders and birth defects in communities near hazardous chemical sites. I. Birth defects and developmental disorders.

Members of the workgroup on birth defects and developmental disorders discussed methods to assess structural anomalies, genetic changes and mutations, fetal and infant mortality, functional deficits, and impaired fetal and neonatal growth. Tier 1 assessments for all five adverse reproductive outcomes consist of questionnaires and reviews of medical records rather than laboratory testing of biologic specimens. The work-group members noted a role for neurodevelopmental testing and for limited genetic studies, such as karyotyping in Tier 2 assessments. Emerging methodologies to identify chromosomal aberrations, DNA adducts, and repair inhibition were reserved for Tier 3.

Environmental arsenic exposure of children around a former copper smelter site.

Arsenic residues in the communities surrounding former smelters remain a public health concern, especially for infants and children. To evaluate environmental exposure among these children, a population-based cross-sectional study was conducted in the vicinity of a former copper smelter in Anaconda, Montana. A total of 414 children less than 72 months old were recruited. First morning voided urine samples and environmental samples were collected for arsenic measurements. The geometric mean of speciated urinary arsenic was 8.6 microg/liter (GSD = 1.7, N = 289). Average arsenic levels of different types of soil ranged from 121 to 236 microg/g and were significantly related to proximity and wind direction to the smelter site. The same significant relationship was observed for interior dust arsenic. Speciated urinary arsenic was found to be significantly related to soil arsenic in bare areas in residential yards (P < 0.0005). In general, elevated excretion of arsenic was demonstrable and warranted parents' attention to reduce exposure of their children to environmental arsenic.

The relationship between surface dust lead loadings on carpets and the blood lead of young children.

The final clean-up of residential lead abatement projects in federally-supported housing, as well as in other housing in a number of states, must meet surface dust lead clearance levels expressed as µg of lead per square foot. These clearance levels were established because hand-to-mouth ingestion of lead-contaminated dust is recognised as a major pathway through which many children are exposed. A dilemma exists because many floors in housing undergoing abatement are carpeted and the established clearance levels are generally not recommended for use on carpets. These clearance levels are also used as 'action levels' to determine whether exposure reduction activities are needed. The US Environmental Protection Agency is currently in the process of issuing standards for hazardous levels of lead in interior dust and bare soil under Title X of the Housing and Community Development Act of 1992, 'The Residential Lead-Based Paint Hazard Reduction Act of 1992'. An effort to develop a potential surface dust lead clearance level for carpets was made using an existing vacuum dust collection method that has previously been shown to be a reliable indicator of childhood lead exposure. This method was designed for use on carpeted and non-carpeted surfaces. Using data from the Cincinnati Soil Lead Abatement Demonstration Project, the suggested floor-dust lead level where an estimated 95% of the population of children would be expected to have blood lead values below the national goal of 10 µg dL(-1), was more than an order of magnitude lower than the current floor-dust lead clearance level of 1080 µg m(-2) (100 µg ft(-2)). Further comparisons of blood lead and carpet lead levels in other parts of the country should be performed before a risk-based lead loading clearance level is established.

Functional implications of postural disequilibrium due to lead exposure.

Measurement of postural equilibrium has been employed as an indirect indicator of functional status of the nervous systems of 109 children (mean age: 5.8 +/- 0.78 years) from the Cincinnati Lead Program Project. The geometric mean blood lead for the first five years of life (PbB05) was 11.9 +/- 1.5 micrograms/dL. Postural sway associated with upright balance was noninvasively quantitated with a microprocessor-based force platform and four tasks performed for 30 sec each by the subjects. A covariate-adjusted multiple regression analysis showed statistically significant associations between PbB05 and the postural sway for the task requiring primarily vestibular and/or proprioceptive systems input, implying potential functional impairment. These findings raised several new issues which are addressed here: (1) A dynamic task has been developed to further test the effect of perturbing those afferents' functional capabilities. (2) A method has been developed to quantitate the stability boundary of each subject to better characterize the limits of functionally-safe postural sway. (3) There is a need to perform the postural sway in a shorter duration than 30 sec so that children younger than five years of age can be tested for early identification of Pb-induced functional impairment of postural equilibrium.

The developmental consequences of low to moderate prenatal and postnatal lead exposure: intellectual attainment in the Cincinnati Lead Study Cohort following school entry.

In a further follow-up study of the Cincinnati Lead Study Cohort, 253 children were administered the Wechsler Intelligence Scale for Children-Revised (WISC-R) at approximately 6.5 years of age. Postnatal blood lead concentrations were inversely associated with Full-Scale (FSIQ) and Performance IQ (PIQ). Following statistical adjustment for developmental co-factors such as maternal IQ and an assessment of the quality of caretaking in the home environment, a statistically significant relationship remained between postnatal blood lead concentrations and PIQ. Further statistical analyses suggested that averaged lifetime blood lead concentrations in excess of 20 micrograms/dL were associated with deficits in PIQ on the order of approximately 7 points when compared to children with mean concentrations less or equal to 10 micrograms/dL. These results are discussed in terms of their consistency with other similar studies as well as their internal consistency with earlier reports on this cohort. The findings of this investigation support recent initiatives in the United States to reduce the exposure of children to environmental lead.

Role of exposure databases in epidemiology.

At present, exposure databases record data primarily for regulatory purposes; they have not focused on serving the needs of epidemiologists or public health. However, the modification of exposure databases could facilitate their use in epidemiology. Characteristics necessary to enhance the use of all databases include easy access by users; documentation of methods, sampling bias, error, and inconsistences; widespread coverage in time and space; and methods and measures for estimating exposure of individuals as well as populations. Also needed are exposure scenarios and models to estimate exposures for geographic areas and time intervals not currently sampled. Multidisciplinary teams are needed to examine current databases, to review strategies for improving data collection, and to suggest and help implement appropriate changes. A long-term goal is to develop and validate data from exposure scenarios and models using data on the relationship of exposure to doses measured in humans.

Lead exposure and growth in the early preschool child: a follow-up report from the Cincinnati Lead Study.

This report is a follow-up of an earlier study of the effects of low to moderate prenatal and postnatal lead exposure on children's growth in stature. Two hundred thirty-five subjects were assessed every 3 months for lead exposure (blood lead level) and stature (recumbent length) up to 33 months of age. Fetal lead exposure was indexed by maternal blood lead level during pregnancy. The adverse effects of lead on growth during the first year of life were reported previously. This analysis covers essentially the second and third years of life. The results indicate that mean blood lead level during this period was negatively associated with attained height at 33 months of age (P = .002). This association was, however, evidenced only among those children who had mean blood lead levels greater than the cohort median (greater than or equal to 10.77 micrograms/dL) during the 3- to 15-month interval. The results also suggest that the effect of lead exposure (both in utero as well as during the first year of life) are transient provided that subsequent exposure to lead is not excessive. It appears that maintaining an average blood lead level of 25 micrograms/dL or more during the second and third year of life was detrimental to the child's attained stature at 33 months of age. Approximately 15% of this cohort experienced these levels of lead exposure. Continued follow-up of this cohort will reveal whether these lead-related deficits persist and whether they continue to be dependent on the level of exposure in an earlier period.

Serum vitamin D metabolites and bone mineralization in young children with chronic low to moderate lead exposure.

One hundred five children (49 male, 99 black) with known lead exposure indices from birth and adequate nutrient intake of calcium, phosphorus, and vitamin D were studied at 1 of 3 ages (21, 27, or 33 months) to determine the effects of chronic low to moderate lead exposure on circulating concentrations of vitamin D metabolites and bone mineral content as determined by photon absorptiometry. Univariate multiple regression analyses showed no direct relationship of blood lead levels to vitamin D metabolites or bone mineral content. Structural equation analyses which took into account potential covariates of age, season, race, and sex showed estimated declines in serum concentrations of total calcium (from 9.72 to 9.61 mg/dL), phosphorus (from 5.4 to 4.67 mg/dL), and 25-hydroxyvitamin D (from 27.24 to 25.8 ng/mL) and estimated increases in concentrations of parathyroid hormones (from 73.03 to 83.14 microL Eq/mL), 1,25-dihydroxyvitamin D (from 62.39 to 62.69 pg/mL), and bone mineral content (from 222.66 to 234.91 mg/cm) over the observed range of average lifetime blood lead concentrations (4.76 to 23.61 micrograms/dL, geometric mean 9.74 micrograms/dL). However, the only statistically significant effect of average lifetime blood lead concentration was that for phosphorus, and the multivariate test of the combined effects of lead on these six outcomes was not statistically significant (P = .2). It is concluded that significant alterations in vitamin D metabolism, calcium and phosphorus homeostasis, and bone mineral content are not present in children whose nutritional status is adequate and who experience low to moderate lead exposure.

Lead exposure and the cognitive development of urban preschool children: the Cincinnati Lead Study cohort at age 4 years.

The purpose of this analysis was to determine if significant associations could be observed between prenatal/postnatal blood lead (PbB) levels and the cognitive development of 258 urban, inner-city children at 4 years of age. These children have been followed since birth with frequent assessments of general health, PbB, and neuropsychological status. The Kaufman Assessment Battery for Children (K-ABC) was administered at approximately 4 years of age. Higher neonatal PbB levels were associated with poorer performance on all K-ABC subscales. However, this inverse association was limited to children from the poorest families. Maternal PbB levels were unrelated to 4-year cognitive status. Few statistically significant associations between postnatal PbB levels and K-ABC scales could be found. However, the results did suggest a weak inverse relationship between postnatal PbB levels and performance on a K-ABC subscale which assesses visual-spatial and visual-motor integration skills. In these results we note both contradiction and accord with previously published prospective studies.

Lead exposure and neurobehavioral development in later infancy.

A prospective methodology was used to assess the neurobehavioral effects of fetal and postnatal lead exposure during the first 2 years of life. Lead was measured in whole blood prenatally in mothers and at quarterly intervals in the infant. Prenatal blood lead levels were low (mean = 8.0 micrograms/dL). However, approximately 25% of the study infants had at least one serial blood lead level of 25 micrograms/dL or higher during the second year of life. Multiple regression and structural equation analyses revealed statistically significant relationships between prenatal and neonatal blood lead level and 3- and 6-month Bayley Mental and/or Psychomotor Development Index. However, by 2 years of age, no statistically significant effects of prenatal or postnatal lead exposure on neurobehavioral development could be detected. Data consistent with the hypothesis that a postnatal neurobehavioral growth catch-up occurred in infants exposed fetally to higher levels of lead are presented.

Lead effects on postural balance of children.

The postural sway responses of 63 children with a mean age of 5.74 years were quantified with a Force Platform technique. The average maximum (max) blood lead (PbB) of these children during the first 5 years of life was 20.7 micrograms/dL (range 9.2 to 32.5). The backward stepwise regression analysis for sway area response during the eyes-closed, no-foam test with all the covariates and confounders and the PbB parameters showed a significant relationship with peak or max PbB during the second year of life. These results are consistent with our previous study with a smaller group of children. The data have been analyzed to provide some insight into the role of various afferent for the maintenance of postural balance. The results suggests a hypothesis that if the max PbB had caused some level of impairment in the functional capacities or interconnectivity of the vestibular and/or proprioception systems at 2 years of age, then it is reasonable to assume that the redundancy in the postural afferent systems would naturally adapt to rely more on the remaining intact afferent system (in this case, vision).

Fetal and infant lead exposure: effects on growth in stature.

The growth of a cohort of 260 infants was prospectively followed up from birth. Blood lead and stature measurements were obtained every 3 months until 15 months of age. Fetal lead exposure was indexed by measuring lead in maternal blood during pregnancy. A longitudinal analysis revealed that covariate adjusted growth rates in stature were negatively related to the infants' postnatal blood lead concentration, as indexed by increase in average blood lead values from 3 to 15 months. However, this relationship between growth rate and change in blood lead concentration was evidenced only among those infants whose mothers had prenatal blood lead levels greater than the maternal cohort median of 7.7 micrograms/dL is about 2 cm shorter at 15 months of age if, postnatally, the infant incurred a 10-micrograms/dL blood lead increase during the 3- to 15-month interval of life, compared with an infant who has no increase.

Mechanisms by which lead depresses linear and ponderal growth in weanling rats.

Lead is known to reduce linear and ponderal growth in children, even at levels of exposure common in the general population. The mechanism involved is not known. The present study was conducted in order to establish the role of food consumption and insulin-like growth factor (IGFI), also commonly known as somatomedin C (SmC), in lead-induced reduction in growth in weanling rats. A further purpose was to test the hypothesis that depressed growth could be prevented by administration of growth hormone and thyroxine, a procedure which prevents arrested growth due to hypophysectomy. Treatment with growth hormone in combination with thyroxine had no effect on depressed growth or food consumption. The reduction in linear and ponderal growth due to lead (approximately 17%) could be largely though not completely accounted for on the basis of reduced food consumption, apparently by a mechanism not involving growth hormone or thyroxine (see above). Plasma SmC was reduced in proportion to reduced food intake, regardless of whether due to Pb or to restriction of food intake in a pair-feeding experiment thereby ruling out an effect of lead on SmC synthesis or activity other than through reduced food consumption. The experiments leading to these conclusions all involved administration of lead in the drinking water, suggesting the possibility that reduced food consumption was peripherally mediated as a result of contact of lead with appetite-depressant receptors in the gastrointestinal tract, e.g., taste receptors. An additional experiment therefore was conducted comparing food consumption and growth resulting from oral lead administration to subcutaneous administration. Similar depressant effects on food consumption and growth resulted at similar concentrations of lead and zinc protoporphyrin in blood. These effects were significantly greater following oral administration, however, suggesting that lead depresses appetite by both a systemic mechanism and one operating at the level of the gastrointestinal tract.

Anodic stripping voltammetry procedure modified for improved accuracy of blood lead analysis.

In evaluating the accuracy and reliability of blood lead (PbB) measurements with the Environmental Science Associates Model 3010A Trace Metal Analyzer, intralaboratory comparison demonstrated that use of the operating conditions recommended by the manufacturer resulted in consistently underestimated PbB concentrations less than 400 micrograms/L and overestimated PbB values greater than 400 micrograms/L. At PbB concentrations less than 50 micrograms/L, measured concentrations were often registered as negative results. However, these negative values could be replicated to within +/- 10 micrograms/L, indicating good precision of the method, but obviously not good accuracy. In addition, lower-than-expected lead (Pb) values were measured in samples containing increased concentrations of copper (Cu), such as may occur in pregnant women. We modified the procedure to eliminate these inaccuracies by substituting manual peak-height measurements for reliance on the integrator and digital display of the instrument. We established the accuracy of the modified procedure by using calibration standards previously quantified by isotope dilution-mass spectroscopy. A quality-control program for monitoring PbB analysis is also described.

Low-level fetal lead exposure effect on neurobehavioral development in early infancy.

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 micrograms/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.