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Biomedical subjects

R L Bornschein

Publications and source records attributed to R L Bornschein.

At least 19 recordsLinked to original sources

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.

Body Height

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.

Bone Density

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.

Child Behavior

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).

Afferent Pathways

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.

Age Factors

Influence of social factors on lead exposure and child development.

A brief overview of current views of child development is provided, with particular attention given to the role the child's physical and social environment plays in influencing the developmental process. Examples from the recent literature are used to illustrate how these factors can influence lead exposure and most importantly how they might interact with lead to ameliorate or exacerbate possible lead effects. An example is provided which demonstrates that failure to control adequately and to adjust the data statistically to correct for the influence of these factors can lead one erroneously to attribute cognitive and behavioral changes to lead. Finally, data from the Cincinnati Prospective Lead Study are presented to illustrate the application of structural equation modeling as a means for unraveling the complex web of sociodemographic, environmental and behavioral influences on childhood lead exposure. The latter analysis indicates that for children less than 24 months of age, lead-containing dust in the home and on the children's hands are important determinates of their blood lead levels. This relationship is influenced by the amount of maternal involvement with their child and other indices of interaction between the child and primary caregiver.

Child

Drug induced activity in lead-exposed mice.

Three interrelated studies were conducted to examine the locomotor activity of lead-exposed mice. The effects of lead were examined as a function of the dose and duration of exposure. Exposure during the first three weeks occurred via the maternal milk supply. Exposure following weaning was achieved via the water supply. Mice received challenges with various pharmaceutical agents, including d-amphetamine, methylphenidate, apomorphine and phenobarbital. The spontaneous activity prior to injection and the drug-induced activity were monitored. Lead-exposed mice usually displayed spontaneous activity which was indistinguishable from that of the control animals. In only one set of observations did lead exposure result in a modest increase in spontaneous activity. The drug-induced activity varied in a complex manner as a function of the magnitude and duration of the lead exposure. Depressed body weight, which was concurrent with high lead exposure (0.5% Pb(Ac)2) was also a significant parameter affecting both the spontaneous and drug-induced activity.

Age Factors

Evaluation of teratogenicity and behavioral toxicity with inhalation exposure of maternal rats to trichloroethylene.

Female rats were exposed by inhalation to trichloroethylene (TCE) vapors at a concentration of 1800 +/- 200 ppm to determine whether exposure before mating and during pregnancy is more detrimental to reproductive outcome than exposure either before mating alone or during pregnancy alone. Four treatment groups were utilized in a two by two factorial design: exposure to TCE for 2 weeks before mating and during the first 20 days of pregnancy; TCE before mating and filtered air during pregnancy; filtered air before mating and TCE during pregnancy; and filtered air before and during pregnancy. Significant elevations in skeletal and soft tissue anomalies, indicative of developmental delay in maturation rather than teratogenesis, were observed in the group exposed during pregnancy alone. The mixed function oxidase enzymes, ethoxycoumarin and ethoxyresorufin, indicative of cytochrome P-450 and P-448 activities, respectively, were measured in maternal and fetal livers, as well as livers of non-pregnant females, and showed variable levels of activity not uniformly related to treatment or pregnancy. Behavioral evaluation of offspring indicated a lack of treatment effect in tests of general activity levels at 10, 20 and 100 days of age. However, a reduction in postnatal body weights was seen in offspring from mothers with pregestational exposure. No results indicative of treatment-related maternal toxicity, embryotoxicity, severe teratogenicity or significant behavioral deficits were obtained in any of the treatment groups.

Abnormalities, Drug-Induced

Brain lipofuscin concentration and oxidant defense enzymes in lead-poisoned neonatal rats.

Neonatal rats were given aqueous lead acetate intragastrically from d 2-20 of life at doses of 0, 10, 50, and 225 mg Pb/kg.d. Blood Pb concentrations on d 21 were (mean +/- SE) 23 +/- 3 (control), 63 +/- 19, 246 +/- 55, and 994 +/- 223 microgram/100 ml, and brain Pb concentrations were 14 +/- 2, 60 +/- 5, 114 +/- 15, and 275 +/- 26 microgram/100 g, respectively. Growth was significantly depressed only in rats given the highest dose of Pb (225 mg/kg.d). Solvent-extractable lipofuscin pigment concentration of brain tissue progressively decreased over the 21-d duration of the experiment but was not significantly altered at any dose of Pb. Brain glutathione peroxidase, glucose-6-phosphate dehydrogenase, and 6-phosphogluconate dehydrogenase activities were stimulated on d 20 at the maximal dose of Pb, but the activities of brain superoxide dismutases and catalase were not altered by Pb exposure. Locomotor activity was significantly increased in the male animals on d 20, but only at the highest dose of Pb. These results indicate that Pb toxicity in neonatal rats is not associated with accelerated in vivo lipid peroxidation in the brain, but that certain oxidant defense mechanisms in the brain are stimulated by Pb.

Aging

Behavioral deficits in adult rats following neonatal lead exposure.

Rats exposed to lead via the maternal milk were tested at maturity on three different visual discrimination tasks. Starting at parturition the dams were given either tap water, 0.20% sodium acetate, 0.02% lead acetate, or 0.20% lead acetate in the drinking water. At weaning, the pups from all the groups were placed on normal chow and tap water. At 20 days of age, the concentration of lead in the blood and brain of the high lead-exposed offspring was approximately 6 times that of controls (11 microgram% vs 66 microgram%). A significant deficit was found in the ability of the high lead-exposed group to acquire a simultaneous visual discrimination task conducted in an operant chamber. No significant differences were observed in the ability of lead-exposed rats to acquire either a successive visual discrimination task or a cued go/no-go discrimination. Thee results suggest that early lead exposure can affect certain behavioral processes and that the effects may persist even after the rat has reached maturity.

Animals

Behavioral effects of low level neonatal lead exposure.

Rats exposed to lead via maternal milk were tested at various stages of development on a number of behavioral tasks. Beginning at paturition, the dams were given either tap water, 0.02%, or 0.10% lead acetate in the drinking water. Pups from all three groups were weaned to normal chow and tap water at 21 days of age. The mean lead concentration of the dam's blood and of neonatal (20 days of age) brain and blood were all below 50 microgram/100 ml. No significant differences were found between the high lead-exposed group and controls in general as measured by wheel running over a 21 day period beginning at 30 days of age. However, there was a significant difference in wheel running behavior during the first three hr of testing. Both lead-exposed groups were found to display significantly less aggressive behavior as measured by the shock-elicited aggression test. Low level lead exposure had no discernable effect on the acquisition and subsequent reversal of a successive brightness discrimination task. Lead exposure under these conditions appears to affect some aspects of emotional behavior, while having little effect on general activity or cognitive function.

Aggression

Diurnal variations in the analgesic effectiveness of morphine in mice.

Response to thermal stimulation and the analgesic effectiveness of morphine during various phases of the diurnal cycle were assessed by the hotplate method. Saline treated controls exhibited shortest reaction times during the last quarter of the light-phase and first quarter of the dark phase. Longest reaction times were recorded during the last quarter of the dark phase. Doses of 4, 8, 16, and 32 mg/kg of morphine was administered IP at the peak and trough of the pain sensitivity rhythm. The ED50 (95% C.L.) during the last quarter of the light phase was found to be 14.60 (10.6-20.0) mg/kg while during the last quarter of the dark phase the ED50 was found to be 5.85 (4.5-7.7) mg/kg. In a second experiment, independent groups of ten mice each were injected SC with 8 mg/kg of morphine at three hr intervals over a 48 hr test session. Peak analgesic activity was obtained in the group injected during the last quarter of the dark phase while minimal analgesic effectiveness was obtained during the third quarter of the light phase. Central administration of morphine via the intraventricular route yielded the same relationship, i.e., maximal analgesic effectiveness during the last quarter of the dark phase.

Analgesia

Technique for assessing visual discrimination learning in mice.

An automated technique for the study of visual discrimination learning in mice has been developed. The technique utilizes a nose-poke as the operant response. The nose-poke response requires no shaping, has a relatively high operant level and can be used to measure preacquisition exploratory behavior. CD-1 mice acquired a simultaneous brightness discrimination readily but a successive brightness discrimination proved more difficult. A 20 sec intertrial interval was optimal for acquisition of the simultaneous discrimination. Reversal learning was slow. This procedure should prove useful in the study of the effects of pharmacologic and toxic agents on learning and performance in both weanlings and adult mice.

Animals

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.

Child, Preschool