A Child with Chronic Manganese Exposure from Drinking Water

The patient's family bought a home in a suburb, but the proximity of the house to wetlands and its distance from the town water main prohibited connecting the house to town water. The family had a well drilled and they drank the well water for 5 years, despite the fact that the water was turbid, had a metallic taste, and left an orange-brown residue on clothes, dishes, and appliances. When the water was tested after 5 years of residential use, the manganese concentration was elevated (1.21 ppm; U.S. Environmental Protection Agency reference, < 0.05 ppm). The family's 10-year-old son had elevated manganese concentrations in whole blood, urine, and hair. The blood manganese level of his brother was normal, but his hair manganese level was elevated. The patient, the 10-year-old, was in the fifth grade and had no history of learning problems; however, teachers had noticed his inattentiveness and lack of focus in the classroom. Our results of cognitive testing were normal, but tests of memory revealed a markedly below-average performance: the patient's general memory index was at the 13th percentile, his verbal memory at the 19th percentile, his visual memory at the 14th percentile, and his learning index at the 19th percentile. The patient's free recall and cued recall tests were all 0.5-1.5 standard deviations (1 SD = 16th percentile) below normal. Psychometric testing scores showed normal IQ but unexpectedly poor verbal and visual memory. These findings are consistent with the known toxic effects of manganese, although a causal relationship cannot necessarily be inferred

Lead, Diabetes, Hypertension, and Renal Function: The Normative Aging Study

In this prospective study, we examined changes in renal function during 6 years of follow-up in relation to baseline lead levels, diabetes, and hypertension among 448 middle-age and elderly men, a subsample of the Normative Aging Study. Lead levels were generally low at baseline, with mean blood lead, patella lead, and tibia lead values of 6.5 μg/dL, 32.4 μg/g, and 21.5 μg/g, respectively. Six percent and 26% of subjects had diabetes and hypertension at baseline, respectively. In multivariate-adjusted regression analyses, longitudinal increases in serum creatinine (SCr) were associated with higher baseline lead levels but these associations were not statistically significant. However, we observed significant interactions of blood lead and tibia lead with diabetes in predicting annual change in SCr. For example, increasing the tibia lead level from the midpoints of the lowest to the highest quartiles (9–34 μg/g) was associated with an increase in the rate of rise in SCr that was 17.6-fold greater in diabetics than in nondiabetics (1.08 mg/dL/10 years vs. 0.062 mg/dL/10 years; p < 0.01). We also observed significant interactions of blood lead and tibia lead with diabetes in relation to baseline SCr levels (tibia lead only) and follow-up SCr levels. A significant interaction of tibia lead with hypertensive status in predicting annual change in SCr was also observed. We conclude that longitudinal decline of renal function among middle-age and elderly individuals appears to depend on both long-term lead stores and circulating lead, with an effect that is most pronounced among diabetics and hypertensives, subjects who likely represent particularly susceptible groups

Maternal arsenic exposure and impaired glucose tolerance during pregnancy

Background: Accumulating evidence has shown an increased risk of type 2 diabetes in general populations exposed to arsenic, but little is known about exposures during pregnancy and the association with gestational diabetes (GD). Objectives: We studied 532 women living proximate to the Tar Creek Superfund Site to investigate whether arsenic exposure is associated with impaired glucose tolerance during pregnancy. Methods: Blood glucose was measured between 24 and 28 weeks gestation after a 1-hr oral glucose tolerance test (GTT) as part of routine prenatal care. Blood and hair were collected at delivery and analyzed for arsenic using inductively coupled plasma mass spectrometry with dynamic reaction cell. Results: Arsenic concentrations ranged from 0.2 to 24.1 μg/L (ppb) (mean ± SD, 1.7 ±1.5) and 1.1 to 724.4 ng/g (ppb) (mean ± SD, 27.4 ± 61.6) in blood and hair, respectively. One-hour glucose levels ranged from 40 to 284 mg/dL (mean ± SD, 108.7 ± 29.5); impaired glucose tolerance was observed in 11.9% of women when using standard screening criterion (> 140 mg/dL). Adjusting for age, Native-American race, prepregnancy body mass index, Medicaid use, and marital status, women in the highest quartile of blood arsenic exposure had 2.8 higher odds of impaired GTT than women in the lowest quartile of exposure (95% confidence interval, 1.1–6.9) (p-trend = 0.008). Conclusions: Among this population of pregnant women, arsenic exposure was associated with increased risk of impaired GTT at 24–28 weeks gestation and therefore may be associated with increased risk of GD

Levels of Lead in Breast Milk and Their Relation to Maternal Blood and Bone Lead Levels at One Month Postpartum.

Despite the many well-recognized benefits of breast-feeding for both mothers and infants, detectable levels of lead in breast milk have been documented in population studies of women with no current environmental or occupational exposures. Mobilization of maternal bone lead stores has been suggested as a potential endogenous source of lead in breast milk. We measured lead in breast milk to quantify the relation between maternal blood and bone lead levels and breast-feeding status (exclusive vs. partial) among 310 lactating women in Mexico City, Mexico, at 1 month postpartum. Umbilical cord and maternal blood samples were collected at delivery. Maternal breast milk, blood, and bone lead levels were obtained at 1 month postpartum. Levels of lead in breast milk ranged from 0.21 to 8.02 microg/L (ppb), with a geometric mean (GM) of 1.1 microg/L; blood lead ranged from 1.8 to 29.9 microg/dL (GM = 8.4 microg/dL); bone lead ranged from less than 1 to 67.2 microg/g bone mineral (patella) and from less than 1 to 76.6 microg/g bone mineral (tibia) at 1 month postpartum. Breast milk lead was significantly correlated with umbilical cord lead [Spearman correlation coefficient (r$_S$) = 0.36, p less than 0.0001] and maternal blood lead (r$_S$= 0.38, p less than 0.0001) at delivery and with maternal blood lead (r$_S$ = 0.42, p less than 0.0001) and patella lead (r$_S$= 0.15, p less than 0.01) at 1 month postpartum. Mother's age, years living in Mexico City, and use of lead-glazed ceramics, all predictive of cumulative lead exposure, were not significant predictors of breast milk lead levels. Adjusting for parity, daily dietary calcium intake (milligrams), infant weight change (grams), and breast-feeding status (exclusive or partial lactation), the estimated effect of an interquartile range (IQR) increase in blood lead (5.0 microg/dL) was associated with a 33% increase in breast milk lead [95% confidence interval (CI), 24 to 43%], whereas an IQR increase in patella lead (20 microg/g) was associated with a 14% increase in breast milk lead (95% CI, 5 to 25%). An IQR increase in tibia lead (12.0 microg/g) was associated with a 5% increase in breast milk lead (95% CI, -3% to 14%). Our results indicate that even among a population of women with relatively high lifetime exposure to lead, levels of lead in breast milk are low, influenced both by current lead exposure and by redistribution of bone lead accumulated from past environmental exposures

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

Maternal Blood, Plasma, and Breast Milk Lead: Lactational Transfer and Contribution to Infant Exposure

Background: Human milk is a potential source of lead exposure. Yet lactational transfer of lead from maternal blood into breast milk and its contribution to infant lead burden remains poorly understood. Objectives: We explored the dose–response relationships between maternal blood, plasma, and breast milk to better understand lactational transfer of lead from blood and plasma into milk and, ultimately, to the breastfeeding infant. Methods: We measured lead in 81 maternal blood, plasma, and breast milk samples at 1 month postpartum and in 60 infant blood samples at 3 months of age. Milk-to-plasma (M/P) lead ratios were calculated. Multivariate linear, piecewise, and generalized additive models were used to examine dose–response relationships between blood, plasma, and milk lead levels. Results: Maternal lead levels (mean ± SD) were as follows: blood: 7.7 ± 4.0 μg/dL; plasma: 0.1 ± 0.1 μg/L; milk: 0.8 ± 0.7 μg/L. The average M/P lead ratio was 7.7 (range, 0.6–39.8) with 97% of the ratios being > 1. The dose–response relationship between plasma lead and M/P ratio was nonlinear (empirical distribution function = 6.5, p = 0.0006) with the M/P ratio decreasing by 16.6 and 0.6 per 0.1 μg/L of plasma lead, respectively, below and above 0.1 μg/L plasma lead. Infant blood lead level (3.4 ± 2.2 μg/dL) increased by 1.8 μg/dL per 1 μg/L milk lead (p < 0.0001, R2 = 0.3). Conclusions: The M/P ratio for lead in humans is substantially higher than previously reported, and transfer of lead from plasma to milk may be higher at lower levels of plasma lead. Breast milk is an important determinant of lead burden among breastfeeding infants. Citation: Ettinger AS, Roy A, Amarasiriwardena CJ, Smith DR, Lupoli N, Mercado-García A, Lamadrid-Figueroa H, Tellez-Rojo MM, Hu H, Hernández-Avila M. 2014. Maternal blood, plasma, and breast milk lead: lactational transfer and contribution to infant exposure. Environ Health Perspect 122:87–92; http://dx.doi.org/10.1289/ehp.130718

Maternal Fish Consumption, Hair Mercury, and Infant Cognition in a U.S. Cohort

Fish and other seafood may contain organic mercury but also beneficial nutrients such as n-3 polyunsaturated fatty acids. We endeavored to study whether maternal fish consumption during pregnancy harms or benefits fetal brain development. We examined associations of maternal fish intake during pregnancy and maternal hair mercury at delivery with infant cognition among 135 mother–infant pairs in Project Viva, a prospective U.S. pregnancy and child cohort study. We assessed infant cognition by the percent novelty preference on visual recognition memory (VRM) testing at 6 months of age. Mothers consumed an average of 1.2 fish servings per week during the second trimester. Mean maternal hair mercury was 0.55 ppm, with 10% of samples > 1.2 ppm. Mean VRM score was 59.8 (range, 10.9–92.5). After adjusting for participant characteristics using linear regression, higher fish intake was associated with higher infant cognition. This association strengthened after adjustment for hair mercury level: For each additional weekly fish serving, offspring VRM score was 4.0 points higher [95% confidence interval (CI), 1.3 to 6.7]. However, an increase of 1 ppm in mercury was associated with a decrement in VRM score of 7.5 (95% CI, –13.7 to –1.2) points. VRM scores were highest among infants of women who consumed > 2 weekly fish servings but had mercury levels ≤1.2 ppm. Higher fish consumption in pregnancy was associated with better infant cognition, but higher mercury levels were associated with lower cognition. Women should continue to eat fish during pregnancy but choose varieties with lower mercury contamination

Association between 24-Hour Urinary Cadmium and Pulmonary Function among Community-Exposed Men: The VA Normative Aging Study

Background: High levels of cadmium exposure are known to cause emphysema in occupationally exposed workers, but little has been reported to date on the association between chronic environmental cadmium exposure and pulmonary function. Objective: In this study we examined the association between pulmonary function and cadmium body burden in a subcohort of the Normative Aging Study, a community-based study of aging. Methods: We examined 96 men who had cadmium measured in single 24-hr urinary specimens collected in 1994–1995 and who had one to three tests of pulmonary function between 1994 and 2002 (a total of 222 observations). We used mixed-effect models to predict pulmonary function based on individual 24-hr urinary cadmium output, adjusted for age, height, time elapsed from the baseline, and smoking status. We assessed effect modification by smoking status. Results: Among all subjects, a single log-unit increase in baseline urinary cadmium was inversely associated with forced expiratory volume in 1 sec (FEV1) percent predicted [β = −7.56%; 95% confidence interval (CI) −13.59% to −1.53%]; forced vital capacity (FVC) percent predicted (β = −2.70%; 95% CI −7.39% to 1.99%), and FEV1/FVC ratio (β = −4.13%; 95% CI −7.61% to −0.66%). In models including an interaction between urinary cadmium and smoking status, there was a graded, statistically significant reduction in FEV1/FVC ratio across smoking status in association with urinary cadmium. Conclusions: This study suggests that chronic cadmium exposure is associated with reduced pulmonary function, and cigarette smoking modifies this association. These results should be interpreted with caution because the sample size is small, and further studies are needed to confirm our findings

Prenatal Exposure to Mercury: Associations with Global DNA Methylation and Hydroxymethylation in Cord Blood and in Childhood

Background: Mercury is a global pollutant, and prenatal exposure is associated with adverse health effects. To date, no studies have evaluated the association between prenatal mercury exposure and DNA hydroxymethylation, an epigenetic modification important for tissue differentiation and embryonic development. Objectives: We sought to evaluate the association between prenatal mercury exposure and offspring global DNA methylation and hydroxymethylation at birth and test for persistence of the association in childhood. Methods: Within Project Viva, a U.S. prebirth cohort, we examined associations of maternal second trimester red blood cell mercury (RBC-Hg) concentrations with global 5-hydroxymethylcytosine (%-5hmC) and 5-methylcytosine (%-5mC) DNA content in blood collected at birth (n=306), early childhood (n=68; 2.9 to 4.9 y), and midchildhood (n=260; 6.7 to 10.5 y). Results: Median prenatal RBC-Hg concentration was 3.23μg/g [interquartile range (IQR)=3.29]. At birth, median cord blood %-5mC, %-5hmC, and their ratio were 4.95%, 0.22%, and 24.37, respectively. The mean adjusted difference [95% confidence interval (CI)] of blood %-5hmC for a doubling in prenatal RBC-Hg concentration was −0.013% (−0.029, 0.002), −0.031% (−0.056, −0.006), and 0.005% (−0.007, 0.018) at birth, early, and midchildhood, respectively. The corresponding relative adjusted change in the genomic ratio of %-5mC to %-5hmC for a doubling in prenatal RBC-Hg concentration was 4.70% (0.04, 9.58), 22.42% (7.73, 39.11), and 0.73% (−4.18, 5.88) at birth, early, and midchildhood, respectively. No associations were present between prenatal maternal RBC-Hg and %-5mC at any time point. Conclusions: Prenatal mercury exposure was associated with lower %-5hmC genomic content and a corresponding increase in the ratio of %-5mC to %-5hmC in cord blood. This association was persistent in early but not midchildhood blood. Our results demonstrate the potential malleability of epigenetic modifications associated with mercury exposure in utero. https://doi.org/10.1289/EHP146