Population-wide blood lead levels have been decreasing in the United States due to lead control measures begun in the 1970s. Nevertheless, in utero exposure may be continuing, or perhaps even increasing, due to the long half-life of contaminants in maternal bone during pregnancy. Furthermore, there is evidence that levels of lead in plasma, which reflect the available fraction of lead in blood, are not adequately represented by whole-blood lead levels and correlate more closely with bone lead levels. These possibilities deserve intensive investigation in light of the recent accumulation of research demonstrating a neurotoxic effect of lead at progressively low levels of exposure. The new project proposed builds on an on-going NIEHS/Superfund-supported study of lead kinetics during reproduction among women in Mexico. In the major component of this project, 5,700 newly pregnant women will be screened in their first trimester, who meet initial eligibility criteria; they will be followed through pregnancy and birth, measuring blood lead levels, hematocrit, weight, and bone resorption (measured by urinary levels of cross-linked N-telopeptide of type I collagen [NTX]); screening bone lead levels will be measured by K-x-ray fluorescence in postpartum women who meet additional eligibility criteria; a cohort of 900 postpartum women and their infant will be selected to ensure a broad distribution based on level of lead in maternal trabecular bone (the patella); the mother-infant pairs will be followed in a prospective cohort study of neurobehavioral outcomes among the infants. The following Hypotheses will be tested: 1)lead level in maternal trabecular bone (represented by the patella bone) is a predictor of adverse infant mental development after controlling for blood level at birth, infant blood lead levels, maternal IQ, maternal intake of iron, zinc, and calcium, and other potential confounders. The magnitude of this effect is greater in women with higher levels of bone resorption during pregnancy, as reflected by urinary levels of NTX. In the sub-study component of this project, we will screen bone lead levels in 120 women who are trying to become pregnant; select 30 of these women who subsequently become pregnant for a prospective study of plasma lead and whole blood analyses during each trimester and during lactation. Hypothesis 2a will also be tested: In comparison to women with low pre-pregnancy bone lead, women with high pre-pregnancy bone lead will experience a greater increase in plasma lead levels; and Hypothesis 2: The percent increase in plasma lead will be greater than the percent increase in whole blood lead.
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