Black Carbon Exposures,Blood Pressure,and Interactions with Single Nucleotide Polymorphisms in MicroRNA Processing Genes

Background

Black carbon (BC) is a marker of traffic pollution that has been associated with blood pressure (BP), but findings have been inconsistent. MicroRNAs (miRNAs) are emerging as key regulators of gene expression, but whether polymorphisms in genes involved in processing of miRNAs to maturity influence susceptibility to BC has not been elucidated.

Objectives

We investigated the association between BC and BP, as well as potential effect modification by single nucleotide polymorphisms (SNPs) in miRNA processing genes.

Methods

Repeated measures analyses were performed using data from the VA Normative Aging Study. Complete covariate data were available for 789 participants with one to six study visits between 1995 and 2008. In models of systolic and diastolic BP, we examined SNP-by-BC interactions with 19 miRNA-related variants under recessive models of inheritance. Mixed-effects models were adjusted for potential confounders including clinical characteristics, lifestyle, and meteorologic factors.

Results

A 1-SD increase in BC (0.415 μg/m³) was associated with 3.04 mmHg higher systolic (95% confidence interval (CI), 2.29–3.79) and 2.28 mmHg higher diastolic BP (95% CI, 1.88–2.67). Interactions modifying BC associations were observed with SNPs in the DICER, GEMIN4, and DiGeorge critical region-8 (DGCR8) genes, and in GEMIN3 and GEMIN4, predicting diastolic and systolic BP, respectively.

Conclusions

We observed evidence of effect modification of the association between BP and 7-day BC moving averages by SNPs associated with miRNA processing. Although the mechanisms underlying these associations are not well understood, they suggest a role for miRNA genesis and processing in influencing BC effects.     

Maternal Blood Lead Levels and the Risk of Pregnancy-Induced Hypertension: The EDEN Cohort Study

Background

Prior studies revealed associations of environmental lead exposure with risks of hypertension and elevated blood pressure.

Objective

We examined the effect of blood lead levels on blood pressure and the incidence of pregnancy-induced hypertension (PIH) in the second and third trimesters of pregnancy.

Methods

One thousand seventeen pregnant women were enrolled in two French municipalities between 2003 and 2005 for the EDEN (Etude des Déterminants pré et post natals du développement et de la santé de l′ Enfant) cohort study. Blood lead concentrations were measured by atomic absorption spectrometry in mothers between 24 and 28 weeks of gestation.

Results

PIH was diagnosed in 106 subjects (10.9%). Age, parity, weight gain, alcohol, smoking habits, and calcium supplementation were comparable between hypertensive and nonhypertensive women. Lead levels were significantly higher in PIH cases (mean ± SD, 2.2 ± 1.4 μg/dL) than in normotensive patients (1.9 ± 1.2 μg/dL; p = 0.02). Adjustment for potential confounder effects slightly attenuated but did not eliminate the significant association between blood lead levels and the risk of PIH (adjusted odds ratio of PIH = 3.3; 95% confidence interval, 1.1–9.7). We also observed geographic differences in lead exposure and in the incidence of PIH and found significant correlations between blood lead levels and unadjusted as well as adjusted systolic and diastolic blood pressures after 24 weeks of gestation.

Conclusions

These findings confirm the relationship between blood lead levels at mid-pregnancy and blood pressure and suggest that environmental lead exposure may play an etiologic role in PIH.     

Blood and Urine Cadmium,Blood Pressure,and Hypertension: A Systematic Review and Meta-analysis

Background

Cadmium exposure has been inconsistently related to blood pressure.

Objectives

We updated and reevaluated the evidence regarding the relationships of blood cadmium (BCd) and urine cadmium (UCd) with blood pressure (BP) and hypertension (HTN) in nonoccupationally exposed populations.

Data sources and extraction

We searched PubMed and Web of Science for articles on BCd or UCd and BP or HTN in nonoccupationally exposed populations and extracted information from studies that provided sufficient data on population, smoking status, exposure, outcomes, and design.

Data synthesis

Twelve articles met inclusion criteria: eight provided data adequate for comparison, and five reported enough data for meta-analysis. Individual studies reported significant positive associations between BCd and systolic BP (SBP) among nonsmoking women [β = 3.14 mmHg per 1 μg/L untransformed BCd; 95% confidence interval (CI), 0.14–6.14] and among premenopausal women (β = 4.83 mmHg per 1 nmol/L log-transformed BCd; 95% CI, 0.17–9.49), and between BCd and diastolic BP (DBP) among women (β = 1.78 mmHg comparing BCd in the 90th and 10th percentiles; 95% CI, 0.64–2.92) and among premenopausal women (β = 3.84 mmHg per 1 nmol/L log-transformed BCd; 95% CI, 0.86–6.82). Three meta-analyses, each of three studies, showed positive associations between BCd and SBP (p = 0.006) and DBP (p < 0.001) among women, with minimal heterogeneity (I² = 3%), and a significant inverse association between UCd and HTN among men and women, with substantial heterogeneity (I² = 80%).

Conclusion

Our results suggest a positive association between BCd and BP among women; the results, however, are inconclusive because of the limited number of representative population-based studies of never-smokers. Associations between UCd and HTN suggest inverse relationships, but inconsistent outcome definitions limit interpretation. We believe a longitudinal study is merited.     

Childhood Lead Exposure After the Phaseout of Leaded Gasoline: An Ecological Study of School-Age Children in Kampala,Uganda

Background

Tetraethyl lead was phased out of gasoline in Uganda in 2005. Recent mitigation of an important source of lead exposure suggests examination and re-evaluation of the prevalence of childhood lead poisoning in this country. Ongoing concerns persist about exposure from the Kiteezi landfill in Kampala, the country’s capital.

Objectives

We determined blood lead distributions among Kampala schoolchildren and identified risk factors for elevated blood lead levels (EBLLs; ≥ 10 μg/dL).

Analytical approach

Using a stratified, cross-sectional design, we obtained blood samples, questionnaire data, and soil and dust samples from the homes and schools of 163 4- to 8-year-old children representing communities with different risks of exposure.

Results

The mean blood lead level (BLL) was 7.15 μg/dL; 20.5% of the children were found to have EBLL. Multivariable analysis found participants whose families owned fewer household items, ate canned food, or used the community water supply as their primary water source to have higher BLLs and likelihood of EBLLs. Distance < 0.5 mi from the landfill was the factor most strongly associated with increments in BLL (5.51 μg/dL, p < 0.0001) and likelihood of EBLL (OR = 4.71, p = 0.0093). Dust/soil lead was not significantly predictive of BLL/EBLL.

Conclusions

Lead poisoning remains highly prevalent among school-age children in Kampala. Confirmatory studies are needed, but further efforts are indicated to limit lead exposure from the landfill, whether through water contamination or through another mechanism. Although African nations are to be lauded for the removal of lead from gasoline, this study serves as a reminder that other sources of exposure to this potent neurotoxicant merit ongoing attention.     

Black Carbon Exposure,Oxidative Stress Genes,and Blood Pressure in a Repeated-Measures Study

Background

Particulate matter (PM) air pollution has been associated with cardiovascular morbidity and mortality, and elevated blood pressure (BP) is a known risk factor for cardiovascular disease. A small number of studies have investigated the relationship between PM and BP and found mixed results. Evidence suggests that traffic-related air pollution contributes significantly to PM-related cardiovascular effects.

Objectives

We hypothesized that black carbon (BC), a traffic-related combustion by-product, would be more strongly associated with BP than would fine PM [aerodynamic diameter ≤ 2.5 μm (PM_2.5)], a heterogeneous PM mixture, and that these effects would be larger among participants with genetic variants associated with impaired antioxidative defense.

Methods

We performed a repeated-measures analysis in elderly men to analyze associations between PM_2.5 and BC exposure and BP using mixed-effects models with random intercepts, adjusting for potential confounders. We also examined statistical interaction between BC and genetic variants related to oxidative stress defense: GSTM1, GSTP1, GSTT1, NQO1, catalase, and HMOX-1.

Results

A 1-SD increase in BC concentration was associated with a 1.5-mmHg increase in systolic BP [95% confidence interval (CI), 0.1–2.8] and a 0.9-mmHg increase in diastolic BP (95% CI, 0.2–1.6). We observed no evidence of statistical interaction between BC and any of the genetic variants examined and found no association between PM_2.5 and BP.

Conclusions

We observed positive associations between BP and BC, but not between BP and PM_2.5, and found no evidence of effect modification of the association between BC and BP by gene variants related to antioxidative defense.     

HFE H63D Polymorphism as a Modifier of the Effect of Cumulative Lead Exposure on Pulse Pressure: The Normative Aging Study

Background

Cumulative lead exposure is associated with a widened pulse pressure (PP; the difference between systolic and diastolic blood pressure), a marker of arterial stiffness and a predictor of cardiovascular disease. Polymorphisms in the hemochromatosis gene (HFE) have been shown to modify the impact of cumulative lead exposure on measures of adult cognition and cardiac function.

Objectives

We examined whether the HFE mutations modify the impact of lead on PP in community-dwelling older men.

Methods

We examined 619 participants with a total of 1,148 observations of PP from a substudy of bone lead levels (a measure of cumulative exposure, measured by in vivo K-shell X-ray fluorescence) and health in the Normative Aging Study between 1991 and 2001. Linear mixed-effects regression models with random intercepts were constructed.

Results

Of the 619 subjects, 138 and 72 carried the HFE H63D and C282Y variants, respectively. After adjusting for age; education; alcohol intake; smoking; daily intakes of calcium, sodium, and potassium; total calories; family history of hypertension; diabetes; height; heart rate; high-density lipoprotein (HDL); total cholesterol:HDL ratio; and waist circumference, baseline bone lead levels were associated with steeper increases in PP in men with at least one H63D allele (p-interaction = 0.03 for tibia and 0.02 for patella) compared with men with only the wild types or C282Y variant.

Conclusions

The HFE H63D polymorphism, but not the C282Y mutation, appears to enhance susceptibility to the deleterious impact of cumulative lead on PP, possibly via prooxidative or pro-inflammatory mechanisms.     

Long-Term Air Pollution Exposure and Blood Pressure in the Sister Study

Background

Exposure to air pollution has been consistently associated with cardiovascular morbidity and mortality, but mechanisms remain uncertain. Associations with blood pressure (BP) may help to explain the cardiovascular effects of air pollution.

Objective

We examined the cross-sectional relationship between long-term (annual average) residential air pollution exposure and BP in the National Institute of Environmental Health Sciences’ Sister Study, a large U.S. cohort study investigating risk factors for breast cancer and other outcomes.

Methods

This analysis included 43,629 women 35–76 years of age, enrolled 2003–2009, who had a sister with breast cancer. Geographic information systems contributed to satellite-based nitrogen dioxide (NO₂) and fine particulate matter (≤ 2.5 μm; PM_2.5) predictions at participant residences at study entry. Generalized additive models were used to examine the relationship between pollutants and measured BP at study entry, adjusting for cardiovascular disease risk factors and including thin plate splines for potential spatial confounding.

Results

A 10-μg/m³ increase in PM_2.5 was associated with 1.4-mmHg higher systolic BP (95% CI: 0.6, 2.3; p < 0.001), 1.0-mmHg higher pulse pressure (95% CI: 0.4, 1.7; p = 0.001), 0.8-mmHg higher mean arterial pressure (95% CI: 0.2, 1.4; p = 0.01), and no significant association with diastolic BP. A 10-ppb increase in NO₂ was associated with a 0.4-mmHg (95% CI: 0.2, 0.6; p < 0.001) higher pulse pressure.

Conclusions

Long-term PM_2.5 and NO₂ exposures were associated with higher blood pressure. On a population scale, such air pollution–related increases in blood pressure could, in part, account for the increases in cardiovascular disease morbidity and mortality seen in prior studies.

Citation

Chan SH, Van Hee VC, Bergen S, Szpiro AA, DeRoo LA, London SJ, Marshall JD, Kaufman JD, Sandler DP. 2015. Long-term air pollution exposure and blood pressure in the Sister Study. Environ Health Perspect 123:951–958; http://dx.doi.org/10.1289/ehp.1408125     

Blood pressure in relation to concentrations of PCB congeners and chlorinated pesticides

Background

Residents of Anniston, Alabama, live near a Monsanto plant that manufactured polychlorinated biphenyls (PCBs) from 1929 to 1971 and are relatively heavily exposed.

Objectives

The goal of this study was to determine the relationship, if any, between blood pressure and levels of total serum PCBs, several PCB groups with common actions or structure, 35 individual PCB congeners, and nine chlorinated pesticides.

Methods

Linear regression analysis was used to determine the relationships between blood pressure and serum levels of the various contaminants after adjustment for age, body mass index, sex, race, smoking, and exercise in 394 Anniston residents who were not taking antihypertensive medication.

Results

Other than age, total serum PCB concentration was the strongest determinant of blood pressure of the covariates studied. We found the strongest associations for those PCB congeners that had multiple ortho chlorines. We found the associations over the full range of blood pressure as well as in those subjects whose blood pressure was in the normal range. The chlorinated pesticides showed no consistent relationship to blood pressure.

Conclusions

In this cross-sectional study, serum concentrations of PCBs, especially those congeners with multiple ortho chlorines, were strongly associated with both systolic and diastolic blood pressure.     

Influence of Prenatal Lead Exposure on Genomic Methylation of Cord Blood DNA

Background

Fetal lead exposure is associated with adverse pregnancy outcomes and developmental and cognitive deficits; however, the mechanism(s) by which lead-induced toxicity occurs remains unknown. Epigenetic fetal programming via DNA methylation may provide a pathway by which environmental lead exposure can influence disease susceptibility.

Objective

This study was designed to determine whether prenatal lead exposure is associated with alterations in genomic methylation of leukocyte DNA levels from umbilical cord samples.

Methods

We measured genomic DNA methylation, as assessed by Alu and LINE-1 (long interspersed nuclear element-1) methylation via pyrosequencing, on 103 umbilical cord blood samples from the biorepository of the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) study group. Prenatal lead exposure had been assessed by measuring maternal bone lead levels at the mid-tibial shaft and the patella using a spot-source ¹⁰⁹Cd K-shell X-ray fluorescence instrument.

Results

We found an inverse dose–response relationship in which quartiles of patella lead correlated with cord LINE-1 methylation (p for trend = 0.01) and and tibia lead correlated with Alu methylation (p for trend = 0.05). In mixed effects regression models, maternal tibia lead was negatively associated with umbilical cord genomic DNA methylation of Alu (β= −0.027; p = 0.01). We found no associations between cord blood lead and cord genomic DNA methylation.

Conclusions

Prenatal lead exposure is inversely associated with genomic DNA methylation in cord blood. These data suggest that the epigenome of the developing fetus can be influenced by maternal cumulative lead burden, which may influence long-term epigenetic programming and disease susceptibility throughout the life course.     

Blood Pressure,Left Ventricular Geometry,and Systolic Function in Children Exposed to Inorganic Arsenic

Background:

Inorganic arsenic (iAs) is a ubiquitous element present in the groundwater worldwide. Cardiovascular effects related to iAs exposure have been studied extensively in adult populations. Few epidemiological studies have been focused on iAs exposure–related cardiovascular disease in children.

Objective:

In this study we investigated the association between iAs exposure, blood pressure (BP), and functional and anatomical echocardiographic parameters in children.

Methods:

A cross-sectional study of 161 children between 3 and 8 years was conducted in Central Mexico. The total concentration of arsenic (As) species in urine (U-tAs) was determined by hydride generation–cryotrapping–atomic absorption spectrometry and lifetime iAs exposure was estimated by multiplying As concentrations measured in drinking water by the duration of water consumption in years (LAsE). BP was measured by standard protocols, and M-mode echocardiographic parameters were determined by ultrasonography.

Results:

U-tAs concentration and LAsE were significantly associated with diastolic (DBP) and systolic blood pressure (SBP) in multivariable linear regression models: DBP and SBP were 0.013 (95% CI: 0.002, 0.024) and 0.021 (95% CI: 0.004, 0.037) mmHg higher in association with each 1-ng/mL increase in U-tAs (p < 0.025), respectively. Left ventricular mass (LVM) was significantly associated with LAsE [5.5 g higher (95% CI: 0.65, 10.26) in children with LAsE > 620 compared with < 382 μg/L-year; p = 0.03] in an adjusted multivariable model. The systolic function parameters left ventricular ejection fraction (EF) and shortening fraction were 3.67% (95% CI: –7.14, –0.20) and 3.41% (95% CI: –6.44, –0.37) lower, respectively, in children with U-tAs > 70 ng/mL compared with < 35 ng/mL.

Conclusion:

Early-life exposure to iAs was significantly associated with higher BP and LVM and with lower EF in our study population of Mexican children.

Citation:

Osorio-Yáñez C, Ayllon-Vergara JC, Arreola-Mendoza L, Aguilar-Madrid G, Hernández-Castellanos E, Sánchez-Peña LC, Del Razo LM. 2015. Blood pressure, left ventricular geometry, and systolic function in children exposed to inorganic arsenic. Environ Health Perspect 123:629–635; http://dx.doi.org/10.1289/ehp.1307327     

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 > 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.

Citation

Farzan SF, Chen Y, Wu F, Jiang J, Liu M, Baker E, Korrick SA, Karagas MR. 2015. Blood pressure changes in relation to arsenic exposure in a U.S. pregnancy cohort. Environ Health Perspect 123:999–1006; http://dx.doi.org/10.1289/ehp.1408472     

Effect of Calcium Supplementation on Blood Lead Levels in Pregnancy: A Randomized Placebo-Controlled Trial

Background

Prenatal lead exposure is associated with deficits in fetal growth and neurodevelopment. Calcium supplementation may attenuate fetal exposure by inhibiting mobilization of maternal bone lead and/or intestinal absorption of ingested lead.

Objective

Our goal was to evaluate the effect of 1,200 mg dietary calcium supplementation on maternal blood lead levels during pregnancy.

Methods

In a double-blind, randomized, placebo-controlled trial conducted from 2001 through 2003 in Mexico City, we randomly assigned 670 women in their first trimester of pregnancy to ingest calcium (n = 334) or placebo (n = 336). We followed subjects through pregnancy and evaluated the effect of supplementation on maternal blood lead, using an intent-to-treat analysis by a mixed-effects regression model with random intercept, in 557 participants (83%) who completed follow-up. We then conducted as-treated analyses using similar models stratified by treatment compliance.

Results

Adjusting for baseline lead level, age, trimester of pregnancy, and dietary energy and calcium intake, calcium was associated with an average 11% reduction (0.4 μg/dL) in blood lead level relative to placebo (p = 0.004). This reduction was more evident in the second trimester (−14%, p < 0.001) than in the third (−8%, p = 0.107) and was strongest in women who were most compliant (those who consumed ≥ 75% calcium pills; −24%, p < 0.001), had baseline blood lead > 5 μg/dL (−17%, p < 0.01), or reported use of lead-glazed ceramics and high bone lead (−31%, p < 0.01).

Conclusion

Calcium supplementation was associated with modest reductions in blood lead when administered during pregnancy and may constitute an important secondary prevention effort to reduce circulating maternal lead and, consequently, fetal exposure.     

Urinary Concentrations of Parabens and Serum Hormone Levels,Semen Quality Parameters,and Sperm DNA Damage

Background

Parabens are commonly used as antimicrobial preservatives in cosmetics, pharmaceuticals, and food and beverage processing. Widespread human exposure to parabens has been recently documented, and some parabens have demonstrated adverse effects on male reproduction in animal studies. However, human epidemiologic studies are lacking.

Objective

We investigated relationships between urinary concentrations of parabens and markers of male reproductive health in an ongoing reproductive epidemiology study.

Methods

Urine samples collected from male partners attending an infertility clinic were analyzed for methyl paraben (MP), propyl paraben (PP), butyl paraben (BP), and bisphenol A (BPA). Associations with serum hormone levels (n = 167), semen quality parameters (n = 190), and sperm DNA damage measures (n = 132) were assessed using multivariable linear regression.

Results

Detection rates in urine were 100% for MP, 92% for PP, and 32% for BP. We observed no statistically significant associations between MP or PP and the outcome measures. Categories of urinary BP concentration were not associated with hormone levels or conventional semen quality parameters, but they were positively associated with sperm DNA damage (p for trend = 0.03). When urinary BPA quartiles were added to the model, BP and BPA were both positively associated with sperm DNA damage (p for trend = 0.03). Assessment of paraben concentrations measured on repeated urine samples from a subset of the men (n = 78) revealed substantial temporal variability.

Conclusions

We found no evidence for a relationship between urinary parabens and hormone levels or semen quality, although intraindividual variability in exposure and a modest sample size could have limited our ability to detect subtle relationships. Our observation of a relationship between BP and sperm DNA damage warrants further investigation.     

Low-level lead exposure and elevations in blood pressure during pregnancy

Background

Lead exposure is associated with elevated blood pressure during pregnancy; however, the magnitude of this relationship at low exposure levels is unclear.

Objectives

Our goal was to determine the association between low-level lead exposure and blood pressure during late pregnancy.

Methods

We collected admission and maximum (based on systolic) blood pressures during labor and delivery among 285 women in Baltimore, Maryland. We measured umbilical cord blood lead using inductively coupled plasma mass spectrometry. Multivariable models were adjusted for age, race, median household income, parity, smoking during pregnancy, prepregnancy body mass index, and anemia. These models were used to calculate benchmark dose values.

Results

Geometric mean cord blood lead was 0.66 μg/dL (95% confidence interval, 0.61–0.70). Comparing blood pressure measurements between those in the highest and those in the lowest quartile of lead exposure, we observed a 6.87-mmHg (1.51–12.21 mmHg) increase in admission systolic blood pressure and a 4.40-mmHg (0.21–8.59 mmHg) increase in admission diastolic blood pressure after adjustment for confounders. Corresponding values for maximum blood pressure increase were 7.72 (1.83–13.60) and 8.33 (1.14–15.53) mmHg. Benchmark dose lower limit values for a 1-SD increase in blood pressure were < 2 μg/dL blood lead for all blood pressure end points.

Conclusions

A significant association between low-level lead exposures and elevations in maternal blood pressure during labor and delivery can be observed at umbilical blood lead levels < 2 μg/dL.     

A Proton Magnetic Resonance Spectroscopy Study of the Chronic Lead Effect on the Basal Ganglion and Frontal and Occipital Lobes in Middle-Age Adults

Background

Lead is known to be a health hazard to the human brain and nervous system based on data from epidemiologic studies. However, few studies have examined the mechanism or biochemical changes caused by lead in the human brain, although recently some have used magnetic resonance spectroscopy (MRS) to test brain metabolism in vivo.

Objectives

In this study, we used 3-T MRS to investigate brain metabolism in workers chronically exposed to lead and matched nonexposed controls.

Materials

Methods: Twenty-two workers at a lead paint factory served as chronically exposed subjects of this study. These workers did not have any clinical syndromes. Eighteen age- and sex-matched nonexposed healthy volunteers served as controls. We measured blood and bone lead and used a 3-T MRS to measure their levels of brain N-acetyl aspartate (NAA), choline (Cho), and total creatine (tCr). A structural questionnaire was used to collect demographic, work, and health histories and information about their life habits.

Results

All the MRS measures were lower in the lead-exposed group. Increased blood and bone lead levels correlated with declines in Cho:tCr ratios, especially in the occipital lobe, where changes in all gray, subcortical, and white matter were significant. Increases in blood and patella lead in every layer of the frontal lobe correlated with significant decreases in NAA:tCr ratios. One of the strongest regression coefficients was −0.023 (SE = 0.005, p < 0.001), which was found in the NAA:tCr ratio of frontal gray matter.

Discussion

We conclude that chronic exposure to lead might upset brain metabolism, especially NAA:tCr and Cho:tCr ratios. Brain NAA and Cho are negatively correlated to blood and bone lead levels, suggesting that lead induces neuronal and axonal damage or loss. The most significant changes occurred in frontal and occipital lobes, areas in which previous neurobehavioral studies have shown memory and visual performance to be adversely affected by lead toxicity.     

Proton magnetic resonance spectroscopy in adults with childhood lead exposure

Background

Childhood lead exposure adversely affects neurodevelopment. However, few studies have examined changes in human brain metabolism that may underlie known adverse cognitive and behavioral outcomes.

Objective

We examined the association between mean childhood blood lead levels and in vivo brain metabolite concentrations as adults, determined by proton magnetic resonance spectroscopy (MRS) in a birth cohort with documented low-to-moderate lead exposure.

Methods

Adult participants from the Cincinnati Lead Study [n = 159; mean age (± SD), 20.8 ± 0.9 years] completed a quantitative, short-echo proton MRS protocol evaluating seven regions to determine brain concentrations of N-acetyl aspartate (NAA), creatine and phosphocreatine (Cr), cholines (Cho), myo-inositol, and a composite of glutamate and glutamine (GLX). Correlation and multiple linear regression analyses were conducted.

Results

Mean childhood blood lead levels were associated with regionally specific brain metabolite concentrations adjusted for age at imaging and Full-Scale intelligence quotient. Adjusted analyses estimated for a unit (micrograms per deciliter) increase in mean childhood blood lead concentrations, a decrease of NAA and Cr concentration levels in the basal ganglia, a decrease of NAA and a decrease of Cho concentration levels in the cerebellar hemisphere, a decrease of GLX concentration levels in vermis, a decrease of Cho and a decrease of GLX concentration levels in parietal white matter, and a decrease of Cho concentration levels in frontal white matter.

Conclusions

Gray-matter NAA reductions associated with increasing childhood blood lead levels suggest that sustained childhood lead exposure produces an irreversible pattern of neuronal dysfunction, whereas associated white-matter choline declines indicate a permanent alteration to myelin architecture.     

Hydroxylated Metabolites of Polybrominated Diphenyl Ethers in Human Blood Samples from the United States

Background

A previous study from our laboratory showed that polybrominated diphenyl ethers (PBDEs) were metabolized to hydroxylated PBDEs (HO-PBDEs) in mice and that para-HO-PBDEs were the most abundant and, potentially, the most toxic metabolites.

Objective

The goal of this study was to determine the concentrations of HO-PBDEs in blood from pregnant women, who had not been intentionally or occupationally exposed to these flame retardants, and from their newborn babies.

Methods

Twenty human blood samples were obtained from a hospital in Indianapolis, Indiana, and analyzed for both PBDEs and HO-PBDEs using electron-capture negative-ionization gas chromatographic mass spectrometry.

Results

The metabolite pattern of HO-PBDEs in human blood was quite different from that found in mice; 5-HO-BDE-47 and 6-HO-BDE-47 were the most abundant metabolites of BDE-47, and 5′-HO-BDE-99 and 6′-HO-BDE-99 were the most abundant metabolites of BDE-99. The relative concentrations between precursor and corresponding metabolites indicated that BDE-99 was more likely to be metabolized than BDE-47 and BDE-100. In addition, three bromophenols were also detected as products of the cleavage of the diphenyl ether bond. The ratio of total hydroxylated metabolites relative to their PBDE precursors ranged from 0.10 to 2.8, indicating that hydroxylated metabolites of PBDEs were accumulated in human blood.

Conclusions

The quite different PBDE metabolite pattern observed in humans versus mice indicates that different enzymes might be involved in the metabolic process. Although the levels of HO-PBDE metabolites found in human blood were low, these metabolites seemed to be accumulating.     

Hemoglobin, lead exposure, and intelligence quotient: effect modification by the DRD2 Taq IA polymorphism

Background

Anemia and lead exposure remain significant public health issues in many parts of the world, often occurring together. Animal studies suggest that the dopamine D2 receptor (DRD2) mediates the effects of both lead and iron on cognition and behavior.

Objective

We tested the hypothesis that the DRD2 Taq IA polymorphism modifies the effects of lead and hemoglobin on intelligence quotient (IQ) among children.

Methods

Blood lead and hemoglobin were assessed in 717 children 3–7 years of age attending 12 schools in Chennai, India. IQ was determined using the Binet-Kamat scales of intelligence. Genotyping for the DRD2 polymorphism was carried out using a MassARRAY iPLEX platform. Stratified analyses and interaction models, using generalized estimating equations (GEEs), were used to explore interactions between lead and hemoglobin, and DRD2 Taq IA categories [homozygous variant (A1) vs. presence of wild-type allele (A2)].

Results

After we controlled for potential confounders, a one-unit increase in log blood lead was associated with a decrease of 9 IQ points [95% confidence interval (CI), −18.08 to −0.16] in the homozygous-variant children (n = 73) compared with a decrease of 4 IQ points (95% CI, −7.21 to −0.69) among those with the wild-type allele (n = 644). Higher hemoglobin levels were associated with higher IQ in the children who carried the wild-type allele DRD2, but in children homozygous for the variant allele, an increase of 1 g/dL hemoglobin was associated with a decrease in 1.82 points of IQ (95% CI, −5.28 to 1.64; interaction term p-value = 0.02).

Conclusion

The results of this study suggest that the DRD2 Taq IA polymorphism disrupts the protective effect of hemoglobin on cognition and may increase the susceptibility to the deficits in IQ due to lead exposure.     

Associations of Serum Concentrations of Persistent Organic Pollutants with the Prevalence of Periodontal Disease and Subpopulations of White Blood Cells

Background

Persistent organic pollutants (POPs), which are endocrine disruptors that accumulate in adipose tissue, can increase the risk of periodontal disease through the disturbance of the immune system.

Objective

We examined associations of background exposure to POPs with periodontal disease in the general population.

Design

Cross-sectional associations of concentrations of serum POPs with the prevalence of periodontal disease were investigated in 1,234 adults ≥ 20 years of age in the National Health and Nutrition Examination Survey 1999–2002.

Results

Among several POPs, organochlorine (OC) pesticides were most strongly associated with periodontal disease. Adjusted odds ratios across quintiles of OC pesticides were 1.0, 1.3, 1.7, 2.4, and 2.7 (p for trend < 0.01) for the presence in any site of clinical attachment loss ≥ 4 mm and 1.0, 1.7, 2.6, 3.4, and 3.7 (p for trend < 0.01) for the presence of pocket depth ≥ 4 mm. Polychlorinated biphenyls and polychlorinated dibenzo-p-dioxins also showed significant positive associations with one or both definitions of periodontal disease. Results did not materially change when continuous variables of clinical attachment loss or pocket depth were used as outcomes. Although participants with periodontal disease had higher white blood cell and neutrophil counts, neutrophil counts were inversely related to OC pesticides (p for trend < 0.01). These inverse associations did not change after excluding subjects with C-reactive protein ≥ 3 mg/L.

Conclusion

POPs, especially OC pesticides, were positively associated with periodontal disease, possibly through immunomodulation due to OC pesticides.     

Prenatal Phthalate Exposure and Childhood Growth and Blood Pressure: Evidence from the Spanish INMA-Sabadell Birth Cohort Study

Background

Human evidence on the effects of early life phthalate exposure on obesity and cardiovascular disease risks, reported by experimental studies, is limited to a few cross-sectional studies.

Objectives

We evaluated the associations between prenatal phthalate exposure and childhood growth and blood pressure in a Spanish birth cohort study.

Methods

We assessed exposure using the average of two phthalate metabolite spot-urine concentrations collected from the mothers in the first and third pregnancy trimesters (creatinine-adjusted, n = 391). Study outcomes were the difference in age- and sex-specific z-scores for weight between birth and 6 months of age; and repeated age- and sex-specific z-scores for body mass index (BMI) at 1, 4, and 7 years; waist-to-height ratio at 4 and 7 years; and age- and height-specific z-scores for systolic and diastolic blood pressure at 4 and 7 years.

Results

The sum of five high-molecular-weight phthalate metabolites (ΣHMWPm) was associated with lower weight z-score difference between birth and 6 months (β per doubling of exposure = –0.41; 95% CI: –0.75, –0.06) and BMI z-scores at later ages in boys (β = –0.28; 95% CI: –0.60, 0.03) and with higher weight z-score difference (β = 0.24; 95% CI: –0.16, 0.65) and BMI z-scores in girls (β = 0.30; 95% CI: –0.04, 0.64) (p for sex interaction = 0.01 and 0.05, respectively). The sum of three low-molecular-weight phthalates (ΣLMWPm) was not significantly associated with any of the growth outcomes. ΣHMWPm and ΣLMWPm were associated with lower systolic blood pressure z-scores in girls but not in boys.

Conclusions

This study suggests that prenatal phthalate exposure may be associated with postnatal growth and blood pressure in a sex-specific manner. Inconsistencies with previous cross-sectional findings highlight the necessity for evaluating phthalate health effects in prospective studies.

Citation

Valvi D, Casas M, Romaguera D, Monfort N, Ventura R, Martinez D, Sunyer J, Vrijheid M. 2015. Prenatal phthalate exposure and childhood growth and blood pressure: evidence from the Spanish INMA-Sabadell birth cohort study. Environ Health Perspect 123:1022–1029; http://dx.doi.org/10.1289/ehp.1408887