Lead exposure and intelligence in 7-year-old children: the Yugoslavia Prospective Study.

For a prospective study of lead exposure and early development, we recruited pregnant women from a lead smelter town and from an unexposed town in Yugoslavia and followed their children through 7 years of age. In this paper we consider associations between lifetime lead exposure, estimated by the area under the blood lead (BPb) versus time curve (AUC7), and intelligence, with particular concern for identifying lead's behavioral signature. The Wechsler Intelligence Scales for Children-Version III (WISC-III) was administered to 309 7-year-old children, 261 of whom had complete data on intelligence, blood lead, and relevant sociodemographic covariates (i.e., Home Observation for the Measurement of the Environment (HOME), birth weight, gender, sibship size, and maternal age, ethnicity, intelligence, and education). These showed anticipated associations with 7-year intelligence, explaining 41-4% of the variance in Full Scale, Performance, and Verbal IQ. Before covariate adjustment, AUC7 was unrelated to intelligence; after adjustment, AUC7 explained a significant 2.8%-4.2% of the variance in IQ. After adjustment, a change in lifetime BPb from 10 to 30 micro/dl related to an estimated decrease of 4.3 Full Scale IQ points; estimated decreases for Verbal and Performance IQ were 3.4 and 4.5 points, respectively. AUC7 was significantly and negatively related to three WISC-III factor scores: Freedom from Distractibility, Perceptual Organization, and Verbal Comprehension; the association with Perceptual Organization was the strongest. Consistent with previous studies, the IQ/lead association is small relative to more powerful social factors. Findings offer support for lead's behavioral signature; perceptual-motor skills are significantly more sensitive to lead exposure than are the language-related aspects of intelligence.

Consequences of lead exposure and iron supplementation on childhood development at age 4 years.

For a prospective study of lead exposure and early development, we recruited pregnant women from a smelter town and a nonlead-exposed town in Yugoslavia and followed them and their children through age 4. For 332 children seen at age 4, mean scores on the McCarthy Scales General Cognitive Index (GCI) in the exposed and nonexposed towns were 81.3 and 86.6, respectively; geometric mean blood lead concentrations (BPb) were 39.9 and 9.6 micrograms/dl, respectively. Potential confounders included the quality of the HOME environment; maternal age, intelligence, education, and language; birthweight and gender. These showed predictable associations with 4-year intelligence, accounting for 42.7% of the variance in GCI. Following adjustment for these variables and for concurrent Hgb, we found significant independent adverse associations between GCI and BPb's, measured at 6-month intervals since birth. At age 4, BPb accounted for an incremental 3.5% of the variance in GCI, such that the estimated loss in GCI associated with an increase in BPb from 10-25 micrograms/dl was 3.8 points. The Perceptual-Performance subscale of the McCarthy was most sensitive to Pb exposure, a result consistent with findings from prospective studies in Boston and Port Pirie.

Independent effects of lead exposure and iron deficiency anemia on developmental outcome at age 2 years.

For a prospective study of lead exposure, iron status, and infant development, we recruited infants living in a smelter town and a non-lead-exposed town in Kosovo, Yugoslavia. Among 392 infants assessed at age 2 years, the mean Mental Development Index (MDI), Bayley Scales of Infant Development, was 105.2. At age 2 years, geometric mean blood lead concentrations were 35.5 and 8.4 micrograms/dl, respectively, among infants from the exposed and nonexposed towns. After controlling for variables associated with MDI, we found significant independent associations for both blood lead and hemoglobin concentrations. For example, a rise in blood lead concentration at age 2 years from 10 to 30 micrograms/dl was associated with an estimated 2.5 point decrement in MDI (p = 0.03); statistically nonsignificant decrements were associated with blood lead levels measured at birth and at 6, 12, and 18 months of age. A decrease in hemoglobin concentration at 18 months of age from 12 to 10 gm/dl was associated with an estimated 3.4 point decrement in MDI (p = 0.02); the latter association was present in both towns, suggesting that it was due to iron deficiency anemia independent of lead exposure. The findings suggest that the brain is vulnerable to the effects of both lead exposure and anemia before 2 years of age. On a global basis, the developmental consequences of anemia may exceed those of lead exposure.