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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.

It has been suggested that the accumulation of tobacco-derived cadmium (Cd) in the placenta is responsible for the adverse effect of cigarette smoking on infant birthweight. We chose to test this hypothesis; therefore, we studied a population of nonsmoking pregnant women who were exposed to low levels of smelter-derived Cd and a group of nonexposed women. A higher mean placental Cd concentration (p less than .0007) was found in the exposed women (n = 106), compared with those who were not exposed (n = 55); the observed Cd concentrations were comparable to concentrations reported previously for smoking and nonsmoking women, respectively. Least squares multiple regression (controlling for potentially confounding variables) revealed no association between placental Cd and birthweight. It was, therefore, concluded that the effect of smoking on birthweight was not mediated through Cd.

We are prospectively examining the relation between environmental lead exposure and pregnancy outcome in cohorts of women exposed to a wide range of air lead concentrations. Titova Mitrovica, Yugoslavia, is the site of a large lead smelter, refinery, and battery factory. At midpregnancy, 602 women in T. Mitrovica and 900 women in Pristina, a non-lead-exposed control town, were interviewed. Blood was obtained for blood lead (PbB), hemoglobin, erythrocyte protoporphyrin, and serum ferritin measurements. Women were seen again at delivery, at which time maternal and umbilical cord blood samples were obtained. While many demographic and social characteristics were similar across the two towns, women in Pristina were more likely to report employment outside the home, cigarette smoking, and alcohol use during pregnancy. As expected, PbB levels were substantially higher in the smelter town. At midpregnancy, PbB geometric means were 17.1 micrograms/dL in T. Mitrovica and 5.1 micrograms/dL in Pristina; 86% of the pregnant women in T. Mitrovica, compared to 3.4% of those in Pristina, had PbB levels greater than 10 micrograms/dL. Within T. Mitrovica, distance between the home and the smelter was the most important predictor of PbB at mid-pregnancy and delivery. Husband's employment in the lead industry was associated with a significant increase in maternal PbB levels independent of place of residence. Higher maternal serum ferritin concentrations were associated with lower PbB levels, suggesting that dietary iron inhibits lead absorption. Overall, the placenta was a poor barrier to lead; the relationship between maternal PbB and umbilical cord PbB was linear across a wide range of PbB levels.

A study on spontaneous abortions and twinning rate was carried out in a commune with a lead smeltery and in a control commune without a specific source of lead exposure. For a period of 20 years (1961-1980) information on spontaneous abortions was recorded from vital statistics data. Data on twin deliveries were obtained from the birth certificates. The additional information regarding sex of twins, maternal age of delivery and mother's and father's occupations were recorded by an interview. To each twin birth two singleton births were matched by the area of residence and date of birth. Pollution measurements data on lead, zinc and cadmium were also evaluated. The average annual rate of spontaneous abortions in the commune with a lead smeltery was 12/1000 and in the control commune 6.7/1000 fertile women. The cumulative rate of twin births was 2.4/1000 inhabitants in the commune with a lead smeltery and 2.6/1000 inhabitants in the control commune. However, in the commune with a lead smeltery in the area actually exposed to lead the cumulative rate of twin deliveries over 20 years was 1.7/1000 inhabitants and in the rest of the commune it was 2.7/1000 inhabitants. The results indicate a possible interference of lead exposure with reproduction.