Cumulative Lead Exposure and Age at Menopause in the Nurses’ Health Study Cohort

Background: Early menopause has been associated with many adverse health outcomes, including increased risk of cardiovascular disease morbidity and mortality. Lead has been found to be adversely associated with female reproductive function, but whether exposures experienced by the general population are associated with altered age at menopause has not been explored. Objective: Our goal was to assess the association between cumulative lead exposure and age at natural menopause. Methods: Self-reported menopausal status and bone lead concentration measured with K-shell X-ray fluorescence—a biomarker of cumulative lead exposure—were obtained from 434 women participants in the Nurses’ Health Study. Results: The mean (± SD) age at natural menopause was 50.8 ± 3.6 years. Higher tibia lead level was associated with younger age at menopause. In adjusted analyses, the average age of menopause for women in the highest tertile of tibia lead was 1.21 years younger (95% CI: –2.08, –0.35) than for women in the lowest tertile (p-trend = 0.006). Although the number of cases was small (n = 23), the odds ratio for early menopause (< 45 years of age) was 5.30 (95% CI: 1.42, 19.78) for women in the highest tertile of tibia lead compared with those in the lowest tertile (p-trend = 0.006). There was no association between patella or blood lead and age at menopause. Conclusions: Our results support an association between low-level cumulative lead exposure and an earlier age at menopause. These data suggest that low-level lead exposure may contribute to menopause-related health outcomes in older women through effects on age at menopause. Citation: Eum KD, Weisskopf MG, Nie LH, Hu H, Korrick SA. 2014. Cumulative lead exposure and age at menopause in the Nurses’ Health Study Cohort. Environ Health Perspect 122:229–234; http://dx.doi.org/10.1289/ehp.120639

Neuropsychological Measures of Attention and Impulse Control among 8-Year-Old Children Exposed Prenatally to Organochlorines

Background: We previously reported associations between organochlorines and behaviors related to attention deficit hyperactivity disorder among boys and girls at 8 years of age using a teacher’s rating scale for a birth cohort in New Bedford, Massachusetts (USA)

Environmental exposure to polychlorinated biphenyls and p,p\u27-DDE and sperm sex-chromosome disomy

Background: Chromosomal abnormalities contribute substantially to reproductive problems, but the role of environmental risk factors has received little attention. Objectives: We evaluated the association of polychlorinated biphenyl (PCB) and dichlorodiphenyldichloroethylene (p,p´-DDE) exposures with sperm sex-chromosome disomy. Methods: We conducted a cross-sectional study of 192 men from subfertile couples. We used multiprobe fluorescence in situ hybridization (FISH) for chromosomes X, Y, and 18 to determine XX, YY, XY, and total sex-chromosome disomy in sperm nuclei. Serum was analyzed for concentrations of 57 PCB congeners and p,p´-DDE. Poisson regression models were used to calculate incidence rate ratios (IRRs) for disomy by exposure quartiles, controlling for demographic characteristics and semen parameters. Results: The median percent disomy was 0.3 for XX and YY, 0.9 for XY, and 1.6 for total sex-chromosome disomy. We observed a significant trend of increasing IRRs for increasing quartiles of p,p´-DDE in XX, XY, and total sex-chromosome disomy, and a significant trend of increasing IRRs for increasing quartiles of PCBs for XY and total sex-chromosome disomy; however, there was a significant inverse association for XX disomy. Conclusions: Our findings suggest that exposure to p,p´-DDE may be associated with increased rates of XX, XY, and total sex-chromosome disomy, whereas exposure to PCBs may be associated with increased rates of YY, XY, and total sex-chromosome disomy. In addition, we observed an inverse association between increased exposure to PCBs and XX disomy. Further work is needed to confirm these findings

Blood Lead Levels and Serum Insulin-Like Growth Factor 1 Concentrations in Peripubertal Boys

Background: Childhood lead exposure has been associated with growth delay. However, the association between blood lead levels (BLLs) and insulin-like growth factor 1 (IGF-1) has not been characterized in a large cohort with low-level lead exposure. Methods: We recruited 394 boys 8–9 years of age from an industrial Russian town in 2003–2005 and followed them annually thereafter. We used linear regression models to estimate the association of baseline BLLs with serum IGF-1 concentration at two follow-up visits (ages 10–11 and 12–13 years), adjusting for demographic and socioeconomic covariates. Results: At study entry, median BLL was 3 μg/dL (range, < 0.5–31 μg/dL), most boys (86%) were prepubertal, and mean ± SD height and BMI z-scores were 0.14 ± 1.0 and –0.2 ± 1.3, respectively. After adjustment for covariates, the mean follow-up IGF-1 concentration was 29.2 ng/mL lower (95% CI: –43.8, –14.5) for boys with high versus low BLL (≥ 5 μg/dL or < 5 μg/dL); this difference persisted after further adjustment for pubertal status. The association of BLL with IGF-1 was stronger for mid-pubertal than prepubertal boys (p = 0.04). Relative to boys with BLLs < 2 μg/dL, adjusted mean IGF-1 concentrations decreased by 12.8 ng/mL (95% CI: –29.9, 4.4) for boys with BLLs of 3–4 μg/dL; 34.5 ng/mL (95% CI: –53.1, –16.0) for BLLs 5–9 μg/dL; and 60.4 ng/mL (95% CI: –90.9, –29.9) for BLLs ≥ 10 μg/dL. Conclusions: In peripubertal boys with low-level lead exposure, higher BLLs were associated with lower serum IGF-1. Inhibition of the hypothalamic–pituitary–growth axis may be one possible pathway by which lead exposure leads to growth delay

Blood Pressure Changes in Relation to Arsenic Exposure in a U.S. Pregnancy Cohort

Background: Inorganic arsenic exposure has been related to the risk of increased blood pressure based largely on cross-sectional studies conducted in highly exposed populations. Pregnancy is a period of particular vulnerability to environmental insults. However, little is known about the cardiovascular impacts of arsenic exposure during pregnancy. Objectives: We evaluated the association between prenatal arsenic exposure and maternal blood pressure over the course of pregnancy in a U.S. population. Methods: The New Hampshire Birth Cohort Study is an ongoing prospective cohort study in which \u3e 10% of participant household wells exceed the arsenic maximum contaminant level of 10 μg/L established by the U.S. EPA. Total urinary arsenic measured at 24–28 weeks gestation was measured and used as a biomarker of exposure during pregnancy in 514 pregnant women, 18–45 years of age, who used a private well in their household. Outcomes were repeated blood pressure measurements (systolic, diastolic, and pulse pressure) recorded during pregnancy. Results: Using linear mixed effects models, we estimated that, on average, each 5-μg/L increase in urinary arsenic was associated with a 0.15-mmHg (95% CI: 0.02, 0.29; p = 0.022) increase in systolic blood pressure per month and a 0.14-mmHg (95% CI: 0.02, 0.25; p = 0.021) increase in pulse pressure per month over the course of pregnancy. Conclusions: In our U.S. cohort of pregnant women, arsenic exposure was associated with greater increases in blood pressure over the course of pregnancy. These findings may have important implications because even modest increases in blood pressure impact cardiovascular disease risk

Prenatal Organochlorine and Methylmercury Exposure and Memory and Learning in School-Age Children in Communities Near the New Bedford Harbor Superfund Site, Massachusetts

Background: Polychlorinated biphenyls (PCBs), organochlorine pesticides, and methylmercury (MeHg) are environmentally persistent with adverse effects on neurodevelopment. However, especially among populations with commonly experienced low levels of exposure, research on neurodevelopmental effects of these toxicants has produced conflicting results. Objectives: We assessed the association of low-level prenatal exposure to these contaminants with memory and learning. Methods: We studied 393 children, born between 1993 and 1998 to mothers residing near a PCB-contaminated harbor in New Bedford, Massachusetts. Cord serum PCB, DDE (dichlorodiphenyldichloroethylene), and maternal peripartum hair mercury (Hg) levels were measured to estimate prenatal exposure. Memory and learning were assessed at 8 years of age (range, 7–11 years) using the Wide Range Assessment of Memory and Learning (WRAML), age-standardized to a mean ± SD of 100 ± 15. Associations with each WRAML index—Visual Memory, Verbal Memory, and Learning—were examined with multivariable linear regression, controlling for potential confounders. Results: Although cord serum PCB levels were low (sum of four PCBs: mean, 0.3 ng/g serum; range, 0.01–4.4), hair Hg levels were typical of the U.S. fish-eating population (mean, 0.6 μg/g; range, 0.3–5.1). In multivariable models, each microgram per gram increase in hair Hg was associated with, on average, decrements of –2.8 on Visual Memory (95% CI: –5.0, –0.6, p = 0.01), –2.2 on Learning (95% CI: –4.6, 0.2, p = 0.08), and –1.7 on Verbal Memory (95% CI: –3.9, 0.6, p = 0.14). There were no significant adverse associations of PCBs or DDE with WRAML indices. Conclusions: These results support an adverse relationship between low-level prenatal MeHg exposure and childhood memory and learning, particularly visual memory. Citation: Orenstein ST, Thurston SW, Bellinger DC, Schwartz JD, Amarasiriwardena CJ, Altshul LM, Korrick SA. 2014. Prenatal organochlorine and methylmercury exposure and memory and learning in school-age children in communities near the New Bedford Harbor Superfund Site, Massachusetts. Environ Health Perspect 122:1253–1259; http://dx.doi.org/10.1289/ehp.130780

Environmental Exposure to Polychlorinated Biphenyls and p,p´-DDE and Sperm Sex-Chromosome Disomy

Background: Chromosomal abnormalities contribute substantially to reproductive problems, but the role of environmental risk factors has received little attention

Relation of Cumulative Low-Level Lead Exposure to Depressive and Phobic Anxiety Symptom Scores in Middle-Age and Elderly Women

Background: Different lines of evidence suggest that low-level lead exposure could be a modifiable risk factor for adverse psychological symptoms, but little work has explored this relation

Does Living Near a Superfund Site Contribute to Higher Polychlorinated Biphenyl (PCB) Exposure?

We assessed determinants of cord serum polychlorinated biphenyl (PCB) levels among 720 infants born between 1993 and 1998 to mothers living near a PCB-contaminated Superfund site in Massachusetts, measuring the sum of 51 PCB congeners (∑PCB) and ascertaining maternal address, diet, sociodemographics, and exposure risk factors. Addresses were geocoded to obtain distance to the Superfund site and neighborhood characteristics. We modeled log(10)(∑PCB) as a function of potential individual and neighborhood risk factors, mapping model residuals to assess spatial correlates of PCB exposure. Similar analyses were performed for light (mono–tetra) and heavy (penta–deca) PCBs to assess potential differences in exposure pathways as a function of relative volatility. PCB-118 (relatively prevalent in site sediments and cord serum) was assessed separately. The geometric mean of ∑PCB levels was 0.40 (range, 0.068–18.14) ng/g serum. Maternal age and birthplace were the strongest predictors of ∑PCB levels. Maternal consumption of organ meat and local dairy products was associated with higher and smoking and previous lactation with lower ∑PCB levels. Infants born later in the study had lower ∑PCB levels, likely due to temporal declines in exposure and site remediation in 1994–1995. No association was found between ∑PCB levels and residential distance from the Superfund site. Similar results were found with light and heavy PCBs and PCB-118. Previously reported demographic (age) and other (lactation, smoking, diet) correlates of PCB exposure, as well as local factors (consumption of local dairy products and Superfund site dredging) but not residential proximity to the site, were important determinants of cord serum PCB levels in the study community

Outcome-Dependent Sampling: An Efficient Sampling and Inference Procedure for Studies With a Continuous Outcome

To characterize the relation between an exposure and a continuous outcome, the sampling of subjects can be done much as it is in a case-control study, such that the sample is enriched with subjects who are especially informative. In an outcome dependent sampling (ODS) design, observations made on a judiciously chosen subset of the base population can provide nearly the same statistical efficiency as observing the entire base population. Reaping the benefits of such sampling, however, requires use of an analysis that accounts for the ODS design. In this report, the authors examined the statistical efficiency of a plain random sample analyzed with standard methods, compared with that of data collected with an ODS design and analyzed by either of two appropriate methods. In addition, three real datasets were analyzed using an ODS approach. The results demonstrate the improved statistical efficiency obtained by using an ODS approach and its applicability in a wide range of settings. An ODS design, coupled with an appropriate analysis, can offer a cost-efficient approach to studying the determinants of a continuous outcome