Urinary Porphyrin Excretion in Neurotypical and Autistic Children

Background

Increased urinary concentrations of pentacarboxyl-, precopro- and copro-porphyrins have been associated with prolonged mercury (Hg) exposure in adults, and comparable increases have been attributed to Hg exposure in children with autism (AU).

Objectives

This study was designed to measure and compare urinary porphyrin concentrations in neurotypical (NT) children and same-age children with autism, and to examine the association between porphyrin levels and past or current Hg exposure in children with autism.

Methods

This exploratory study enrolled 278 children 2–12 years of age. We evaluated three groups: AU, pervasive developmental disorder-not otherwise specified (PDD-NOS), and NT. Mothers/caregivers provided information at enrollment regarding medical, dental, and dietary exposures. Urine samples from all children were acquired for analyses of porphyrin, creatinine, and Hg. Differences between groups for mean porphyrin and Hg levels were evaluated. Logistic regression analysis was conducted to determine whether porphyrin levels were associated with increased risk of autism.

Results

Mean urinary porphyrin concentrations are naturally high in young children and decline by as much as 2.5-fold between 2 and 12 years of age. Elevated copro- (p < 0.009), hexacarboxyl- (p < 0.01) and pentacarboxyl- (p < 0.001) porphyrin concentrations were significantly associated with AU but not with PDD-NOS. No differences were found between NT and AU in urinary Hg levels or in past Hg exposure as determined by fish consumption, number of dental amalgam fillings, or vaccines received.

Conclusions

These findings identify disordered porphyrin metabolism as a salient characteristic of autism. Hg exposures were comparable between diagnostic groups, and a porphyrin pattern consistent with that seen in Hg-exposed adults was not apparent.     

Placental DNA Methylation Related to Both Infant Toenail Mercury and Adverse Neurobehavioral Outcomes

Background

Prenatal mercury (Hg) exposure is associated with adverse child neurobehavioral outcomes. Because Hg can interfere with placental functioning and cross the placenta to target the fetal brain, prenatal Hg exposure can inhibit fetal growth and development directly and indirectly.

Objectives

We examined potential associations between prenatal Hg exposure assessed through infant toenail Hg, placental DNA methylation changes, and newborn neurobehavioral outcomes.

Methods

The methylation status of > 485,000 CpG loci was interrogated in 192 placental samples using Illumina’s Infinium HumanMethylation450 BeadArray. Hg concentrations were analyzed in toenail clippings from a subset of 41 infants; neurobehavior was assessed using the NICU Network Neurobehavioral Scales (NNNS) in an independent subset of 151 infants.

Results

We identified 339 loci with an average methylation difference > 0.125 between any two toenail Hg tertiles. Variation among these loci was subsequently found to be associated with a high-risk neurodevelopmental profile (omnibus p-value = 0.007) characterized by the NNNS. Ten loci had p < 0.01 for the association between methylation and the high-risk NNNS profile. Six of 10 loci reside in the EMID2 gene and were hypomethylated in the 16 high-risk profile infants’ placentas. Methylation at these loci was moderately correlated (correlation coefficients range, –0.33 to –0.45) with EMID2 expression.

Conclusions

EMID2 hypomethylation may represent a novel mechanism linking in utero Hg exposure and adverse infant neurobehavioral outcomes.

Citation

Maccani JZ, Koestler DC, Lester B, Houseman EA, Armstrong DA, Kelsey KT, Marsit CJ. 2015. Placental DNA methylation related to both infant toenail mercury and adverse neurobehavioral outcomes. Environ Health Perspect 123:723–729; http://dx.doi.org/10.1289/ehp.1408561     

Genetic Effects on Toxic and Essential Elements in Humans: Arsenic,Cadmium, Copper,Lead, Mercury,Selenium, and Zinc in Erythrocytes

Background and objectives

An excess of toxic trace elements or a deficiency of essential ones has been implicated in many common diseases or public health problems, but little is known about causes of variation between people living within similar environments. We estimated effects of personal and socioeconomic characteristics on concentrations of arsenic (As), cadmium (Cd), copper (Cu), mercury (Hg), lead (Pb), selenium (Se), and zinc (Zn) in erythrocytes and tested for genetic effects using data from twin pairs.

Methods

We used blood samples from 2,926 adult twins living in Australia (1,925 women and 1,001 men; 30–92 years of age) and determined element concentrations in erythrocytes by inductively coupled plasma-mass spectrometry. We assessed associations between element concentrations and personal and socioeconomic characteristics, as well as the sources of genetic and environmental variation and covariation in element concentrations. We evaluated the chromosomal locations of genes affecting these characteristics by linkage analysis in 501 dizygotic twin pairs.

Results

Concentrations of Cu, Se, and Zn, and of As and Hg showed substantial correlations, concentrations of As and Hg due mainly to common genetic effects. Genetic linkage analysis showed significant linkage for Pb [chromosome 3, near SLC4A7 (solute carrier family 4, sodium bicarbonate cotransporter, member 7)] and suggestive linkage for Cd (chromosomes 2, 18, 20, and X), Hg (chromosome 5), Se (chromosomes 4 and 8), and Zn {chromosome 2, near SLC11A1 [solute carrier family 11 (proton-coupled divalent metal ion transporters)]}.

Conclusions

Although environmental exposure is a precondition for accumulation of toxic elements, individual characteristics and genetic factors are also important. Identification of the contributory genetic polymorphisms will improve our understanding of trace and toxic element uptake and distribution mechanisms.     

In Inland China,Rice, Rather than Fish,Is the Major Pathway for Methylmercury Exposure

Background

Fish consumption is considered the primary pathway of methylmercury (MeHg) exposure for most people in the world. However, in the inland regions of China, most of the residents eat little fish, but they live in areas where a significant amount of mercury (Hg) is present in the environment.

Objectives

We assessed concentrations of total Hg and MeHg in samples of water, air, agricultural products, and other exposure media to determine the main exposure pathway of Hg in populations in inland China.

Methods

We selected Guizhou Province for our study because it is highly contaminated with Hg and therefore is representative of other Hg-contaminated areas in China. We selected four study locations in Guizhou Province: three that represent typical environments with severe Hg pollution [due to Hg mining and smelting (Wanshan), traditional zinc smelting (recently closed; Weining), and heavy coal-based industry (Qingzhen)], and a village in a remote nature reserve (Leigong).

Results

The probable daily intake (PDI) of MeHg for an adult population based on 60 kg body weight (bw) was considerably higher in Wanshan than in the other three locations. With an average PDI of 0.096 μg/kg bw/day (range, 0.015–0.45 μg/kg bw/day), approximately 34% of the inhabitants in Wanshan exceeded the reference dose of 0.1 μg/kg bw/day established by the U.S. Environmental Protection Agency. The PDI of MeHg for residents in the three other locations were all well below 0.1 μg/kg bw/day (averages from 0.017 to 0.023 μg/kg bw/day, with a maximum of 0.095 μg/kg bw/day). In all four areas, rice consumption accounted for 94–96% of the PDI of MeHg.

Conclusion

We found that rice consumption is by far the most important MeHg exposure route; however, most of the residents (except those in Hg-mining areas) have low PDIs of MeHg.     

Organic and Inorganic Mercury in Neonatal Rat Brain after Prenatal Exposure to Methylmercury and Mercury Vapor

Background

Many populations are exposed to multiple species of mercury (Hg), predominantly organic Hg as methylmercury (MeHg) from fish, and inorganic Hg as Hg vapor from dental amalgams. Most of our knowledge of the neurotoxicity of Hg is based on research devoted to studying only one form at a time, mostly MeHg.

Objectives

In this study we investigated the effects of prenatal exposure to MeHg and Hg vapor on Hg concentrations in the brain of neonatal rats.

Methods

Female Long-Evans hooded rats were exposed to MeHg (0, 3, 6, or 9 ppm as drinking solution), Hg vapor (0, 300, or 1,000 μg/m³ for 2 hr/day), or the combination of both, from 30 days before breeding through gestational day 18. On postnatal day 4, whole brains were taken from one male and one female from each of four litters in each treatment group to assess organic and inorganic Hg in the brain by cold vapor atomic absorption spectrometry.

Results

Statistical analysis using linear mixed effects models showed that MeHg dose was the primary determinant of both organic and inorganic brain Hg levels. For both outcomes, we also found significant interactions between MeHg and Hg vapor exposure. These interactions were driven by the fact that among animals not exposed to MeHg, animals exposed to Hg vapor had significantly greater organic and inorganic brain Hg levels than did unexposed animals.

Conclusion

This interaction, heretofore not reported, suggests that coexposure to MeHg and Hg vapor at levels relevant to human exposure might elevate neurotoxic risks.     

Blood Mercury Concentrations in CHARGE Study Children with and without Autism

Background

Some authors have reported higher blood mercury (Hg) levels in persons with autism, relative to unaffected controls.

Objectives

We compared blood total Hg concentrations in children with autism or autism spectrum disorder (AU/ASD) and typically developing (TD) controls in population-based samples, and determined the role of fish consumption in differences observed.

Methods

The Childhood Autism Risk from Genetics and the Environment (CHARGE) Study enrolled children 2–5 years of age. After diagnostic evaluation, we analyzed three groups: AU/ASD, non-AU/ASD with developmental delay (DD), and population-based TD controls. Mothers were interviewed about household, medical, and dietary exposures. Blood Hg was measured by inductively coupled plasma mass spectrometry. Multiple linear regression analysis was conducted (n = 452) to predict blood Hg from diagnostic status controlling for Hg sources.

Results

Fish consumption strongly predicted total Hg concentration. AU/ASD children ate less fish. After adjustment for fish and other Hg sources, blood Hg levels in AU/ASD children were similar to those of TD children (p = 0.75); this was also true among non-fish eaters (p = 0.73). The direct effect of AU/ASD diagnosis on blood Hg not through the indirect pathway of altered fish consumption was a 12% reduction. DD children had lower blood Hg concentrations in all analyses. Dental amalgams in children with gum-chewing or teeth-grinding habits predicted higher levels.

Conclusions

After accounting for dietary and other differences in Hg exposures, total Hg in blood was neither elevated nor reduced in CHARGE Study preschoolers with AU/ASD compared with unaffected controls, and resembled those of nationally representative samples.     

Adult Women’s Blood Mercury Concentrations Vary Regionally in the United States: Association with Patterns of Fish Consumption (NHANES 1999–2004)

Background

The current, continuous National Health and Nutrition Examination Survey (NHANES) has included blood mercury (BHg) and fish/shellfish consumption since it began in 1999. NHANES 1999–2004 data form the basis for these analyses.

Objectives

This study was designed to determine BHg distributions within U.S. Census regions and within coastal and noncoastal areas among women of childbearing age, their association with patterns of fish consumption, and changes from 1999 through 2004.

Methods

We performed univariate and bivariate analyses to determine the distribution of BHg and fish consumption in the population and to investigate differences by geography, race/ethnicity, and income. We used multivariate analysis (regression) to determine the strongest predictors of BHg among geography, demographic factors, and fish consumption.

Results

Elevated BHg occurred more commonly among women of childbearing age living in coastal areas of the United States (approximately one in six women). Regionally, exposures differ across the United States: Northeast > South and West > Midwest. Asian women and women with higher income ate more fish and had higher BHg. Time-trend analyses identified reduced BHg and reduced intake of Hg in the upper percentiles without an overall reduction of fish consumption.

Conclusions

BHg is associated with income, ethnicity, residence (census region and coastal proximity). From 1999 through 2004, BHg decreased without a concomitant decrease in fish consumption. Data are consistent with a shift over this time period in fish species in women’s diets.     

Pesticide Exposure and Hypertensive Disorders During Pregnancy

Background

Hypertensive disorders of pregnancy, including pregnancy-induced hypertension (PIH) and preeclampsia (PE), complicate 2–8% of pregnancies. Few studies have examined environmental risk factors in relation to these conditions.

Objectives

Our goal was to examine whether pesticide exposure during pregnancy was associated with hypertensive disorders of pregnancy.

Methods

We analyzed self-reported data from 11,274 wives of farmers enrolled in the Agricultural Health Study (AHS) between 1993 and 1997. Using logistic regression models, we estimated the adjusted odds ratios (AORs) for PIH and PE associated with pesticide-related activities during the first trimester of pregnancy.

Results

First-trimester residential and agricultural activities with potential exposure to pesticides were associated with both PIH [residential AOR = 1.27; 95% confidence interval (CI), 1.02–1.60; agricultural AOR = 1.60; 95% CI, 1.05–2.45] and PE (residential AOR = 1.32; 95% CI, 1.02–1.70; agricultural AOR = 2.07; 95% CI, 1.34–3.21).

Conclusions

Exposure to pesticides during pregnancy may increase the risk of hypertensive disorders of pregnancy. Laboratory research may provide insights into relationships between pesticide exposure and hypertensive diseases of pregnancy.     

National Use of Asbestos in Relation to Economic Development

Background

National disparities in asbestos use will likely lead to an unequal burden of asbestos diseases.

Objectives

As economic status may be linked to asbestos use, we assessed, globally, the relationship between indicators of national economic development and asbestos use.

Methods

For the 135 countries that have ever used asbestos, per capita asbestos use (kilograms per capita per year) was compared with per capita gross domestic product (GDP) in 1990 Geary–Khamis dollars (GKD) for the period 1920–2003. Countries were grouped into three income levels (high, middle, and low) that were adapted from the 2003 World Bank categories.

Results

The historical pattern of asbestos use followed the environmental Kuznets curve in which use by high-income countries peaked when incomes attained 10,000–15,000 GKD and essentially ceased at income levels over 20,000 GKD. Currently, middle- and low-income countries are increasing their use of asbestos, closely following the paths once traced by higher income countries.

Conclusions

Developing countries have the opportunity to eliminate asbestos use sooner than high-income countries and thus reduce the future burden of asbestos diseases.     

Selecting Adequate Exposure Biomarkers of Diisononyl and Diisodecyl Phthalates: Data from the 2005–2006 National Health and Nutrition Examination Survey

Background

High-molecular-weight phthalates, such as diisononyl phthalate (DINP) and diisodecyl phthalate (DIDP), are used primarily as polyvinyl chloride plasticizers.

Objectives

We assessed exposure to DINP and DIDP in a representative sample of persons ≥ 6 years of age in the U.S. general population from the 2005–2006 National Health and Nutrition Examination Survey (NHANES).

Methods

We analyzed 2,548 urine samples by using online solid-phase extraction coupled to isotope dilution high-performance liquid chromatography–tandem mass spectrometry.

Results

We detected monocarboxyisooctyl phthalate (MCOP), a metabolite of DINP, and monocarboxyisononyl phthalate (MCNP), a metabolite of DIDP, in 95.2% and 89.9% of the samples, respectively. We detected monoisononyl phthalate (MNP), a minor metabolite of DINP, much less frequently (12.9%) and at concentration ranges (> 0.8 μg/L–148.1 μg/L) much lower than MCOP (> 0.7 μg/L– 4,961 μg/L). Adjusted geometric mean concentrations of MCOP and MCNP were significantly higher (p < 0.01) among children than among adolescents and adults.

Conclusions

The general U.S. population, including children, was exposed to DINP and DIDP. In previous NHANES cycles, the occurrence of human exposure to DINP by using MNP as the sole urinary biomarker has been underestimated, thus illustrating the importance of selecting the most adequate biomarkers for exposure assessment.     

Prenatal Exposure to Lead, δ-Aminolevulinic Acid,and Schizophrenia: Further Evidence

Background

A previously conducted study of prenatal lead exposure and schizophrenia using δ-aminolevulinic acid, a biologic marker of Pb exposure, in archived maternal serum samples collected from subjects enrolled in the Childhood Health and Development Study (1959–1966) based in Oakland, California, suggested a possible association between prenatal Pb exposure and the development of schizophrenia in later life.

Objectives

In the present study we extend these findings using samples collected from the New England cohort of the National Collaborative Perinatal Project (1959–1966). Using similar methods, in this study we found results that suggest a comparable association in this cohort.

Methods

We pooled matched sets of cases and controls from both the California and New England sites using a multilevel random-intercept logistic regression model, accounting for matching and site structure as well as adjusting for maternal age at delivery and maternal education.

Results

The estimated odds ratio for schizophrenia associated with exposure corresponding to 15 μg/dL of blood Pb was 1.92 (95% confidence interval, 1.05–3.87; p = 0.03).

Conclusion

Although several limitations constrain generalizability, these results are consistent with previous findings and provide further evidence for the role of early environmental exposures in the development of adult-onset psychiatric disorders.     

Global Burden of Aflatoxin-Induced Hepatocellular Carcinoma: A Risk Assessment

Background

Hepatocellular carcinoma (HCC), or liver cancer, is the third leading cause of cancer deaths worldwide, with prevalence 16–32 times higher in developing countries than in developed countries. Aflatoxin, a contaminant produced by the fungi Aspergillus flavus and Aspergillus parasiticus in maize and nuts, is a known human liver carcinogen.

Objectives

We sought to determine the global burden of HCC attributable to aflatoxin exposure.

Methods

We conducted a quantitative cancer risk assessment, for which we collected global data on food-borne aflatoxin levels, consumption of aflatoxin-contaminated foods, and hepatitis B virus (HBV) prevalence. We calculated the cancer potency of aflatoxin for HBV-postive and HBV-negative individuals, as well as the uncertainty in all variables, to estimate the global burden of aflatoxin-related HCC.

Results

Of the 550,000–600,000 new HCC cases worldwide each year, about 25,200–155,000 may be attributable to aflatoxin exposure. Most cases occur in sub-Saharan Africa, Southeast Asia, and China where populations suffer from both high HBV prevalence and largely uncontrolled aflatoxin exposure in food.

Conclusions

Aflatoxin may play a causative role in 4.6–28.2% of all global HCC cases.     

Traffic-Related Air Pollution and Incident Type 2 Diabetes: Results from the SALIA Cohort Study

Background

Cross-sectional and ecological studies indicate that air pollution may be a risk factor for type 2 diabetes, but prospective data are lacking.

Objective

We examined the association between traffic-related air pollution and incident type 2 diabetes.

Design

Between 1985 and 1994, cross-sectional surveys were performed in the highly industrialized Ruhr district (West Germany); a follow-up investigation was conducted in 2006 using data from the Study on the Influence of Air Pollution on Lung, Inflammation and Aging (SALIA) cohort.

Participants

1,775 nondiabetic women who were 54–55 years old at baseline participated in both baseline and follow-up investigations and had complete information available.

Materials and Methods

Using questionnaires, we assessed 16-year incidence (1990–2006) of type 2 diabetes and information about covariates. Complement factor C3c as marker for subclinical inflammation was measured at baseline. Individual exposure to traffic-related particulate matter (PM) and nitrogen dioxide was determined at different spatial scales.

Results

Between 1990 and 2006, 87 (10.5%) new cases of diabetes were reported among the SALIA cohort members. The hazards for diabetes were increased by 15–42% per interquartile range of PM or traffic-related exposure. The associations persisted when different spatial scales were used to assess exposure and remained robust after adjusting for age, body mass index, socioeconomic status, and exposure to several non–traffic-related sources of air pollution. C3c was associated with PM pollution at baseline and was a strong independent predictor of incident diabetes. Exploratory analyses indicated that women with high C3c blood levels were more susceptible for PM-related excess risk of diabetes than were women with low C3c levels.

Conclusions

Traffic-related air pollution is associated with incident type 2 diabetes among elderly women. Subclinical inflammation may be a mechanism linking air pollution with type 2 diabetes.

Relevance to clinical practice

Our study identifies traffic-related air pollution as a novel and potentially modifiable risk factor of type 2 diabetes.     

Oxidative Damage to DNA and Lipids as Biomarkers of Exposure to Air Pollution

Background

Air pollution is thought to exert health effects through oxidative stress, which causes damage to DNA and lipids.

Objective

We determined whether levels of oxidatively damaged DNA and lipid peroxidation products in cells or bodily fluids from humans are useful biomarkers of biologically effective dose in studies of the health effects of exposure to particulate matter (PM) from combustion processes.

Data sources

We identified publications that reported estimated associations between environmental exposure to PM and oxidative damage to DNA and lipids in PubMed and EMBASE. We also identified publications from reference lists and articles cited in the Web of Science.

Data extraction

For each study, we obtained information on the estimated effect size to calculate the standardized mean difference (unitless) and determined the potential for errors in exposure assessment and analysis of each of the biomarkers, for total and stratified formal meta-analyses.

Data synthesis

In the meta-analysis, the standardized mean differences (95% confidence interval) between exposed and unexposed subjects for oxidized DNA and lipids were 0.53 (0.29–0.76) and 0.73 (0.18–1.28) in blood and 0.52 (0.22–0.82) and 0.49 (0.01–0.97) in urine, respectively. The standardized mean difference for oxidized lipids was 0.64 (0.07–1.21) in the airways. Restricting analyses to studies unlikely to have substantial biomarker or exposure measurement error, studies likely to have biomarker and/or exposure error, or studies likely to have both sources of error resulted in standardized mean differences of 0.55 (0.19–0.90), 0.66 (0.37–0.95), and 0.65 (0.34–0.96), respectively.

Conclusions

Exposure to combustion particles is consistenly associated with oxidatively damaged DNA and lipids in humans, suggesting that it is possible to use these measurements as biomarkers of biologically effective dose.     

Correlations between Prenatal Exposure to Perfluorinated Chemicals and Reduced Fetal Growth

Background

Perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) are man-made, ubiquitous, and persistent contaminants in the environment, wildlife, and humans. Although recent studies have shown that these chemicals interfere with fetal growth in humans, the results are inconsistent.

Objectives

Our goal was to investigate the correlation between relatively low levels of PFOS and PFOA in maternal serum and birth weight and birth size.

Methods

We conducted a hospital-based prospective cohort study between July 2002 and October 2005 in Sapporo, Japan. A total of 428 women and their infants were involved in the study. We obtained characteristics of the mothers and infants from self-administered questionnaire surveys and from medical records. We analyzed maternal serum samples for PFOS and PFOA by liquid chromatography–tandem mass spectrometry (LC/MS/MS).

Results

After adjusting for confounding factors, PFOS levels negatively correlated with birth weight [per log₁₀ unit: β = −148.8 g; 95% confidence interval (CI), −297.0 to −0.5 g]. In addition, analyses stratified by sex revealed that PFOS levels negatively correlated with birth weight only in female infants (per log₁₀ unit: β = −269.4 g; 95% CI, −465.7 to −73.0 g). However, we observed no correlation between PFOA levels and birth weight.

Conclusion

Our results indicate that in utero exposure to relatively low levels of PFOS was negatively correlated with birth weight.     

Maternal Bisphenol A Exposure Promotes the Development of Experimental Asthma in Mouse Pups

Background

We recently reported that various environmental estrogens induce mast cell degranulation and enhance IgE-mediated release of allergic mediators in vitro.

Objectives

We hypothesized that environmental estrogens would enhance allergic sensitization as well as bronchial inflammation and responsiveness. To test this hypothesis, we exposed fetal and neonatal mice to the common environmental estrogen bisphenol A (BPA) via maternal loading and assessed the pups’ response to allergic sensitization and bronchial challenge.

Methods

Female BALB/c mice received 10 μg/mL BPA in their drinking water from 1 week before impregnation to the end of the study. Neonatal mice were given a single 5 μg intraperitoneal dose of ovalbumin (OVA) with aluminum hydroxide on postnatal day 4 and 3% OVA by nebulization for 10 min on days 13, 14, and 15. Forty-eight hours after the last nebulization, we assessed serum IgE antibodies to OVA by enzyme-linked immunosorbent assay (ELISA) and airway inflammation and hyperresponsiveness by enumerating eosinophils in bronchoalveolar lavage fluid, whole-body barometric plethysmography, and a forced oscillation technique.

Results

Neonates from BPA-exposed mothers responded to this “suboptimal” sensitization with higher serum IgE anti-OVA concentrations compared with those from unexposed mothers (p < 0.05), and eosinophilic inflammation in their airways was significantly greater. Airway responsiveness of the OVA-sensitized neonates from BPA-treated mothers was enhanced compared with those from unexposed mothers (p < 0.05).

Conclusions

Perinatal exposure to BPA enhances allergic sensitization and bronchial inflammation and responsiveness in a susceptible animal model of asthma.     

Urinary Phthalate Metabolites in Relation to Preterm Birth in Mexico City

Background

Rates of preterm birth have been rising over the past several decades. Factors contributing to this trend remain largely unclear, and exposure to environmental contaminants may play a role.

Objective

We investigated the relationship between phthalate exposure and preterm birth.

Methods

Within a large Mexican birth cohort study, we compared third-trimester urinary phthalate metabolite concentrations in 30 women who delivered preterm (< 37 weeks of gestation) with those of 30 controls (≥ 37 weeks of gestation).

Results

Concentrations of most of the metabolites were similar to those reported among U.S. females, although in the present study mono-n-butyl phthalate (MBP) concentrations were higher and monobenzyl phthalate (MBzP) concentrations lower. In a crude comparison before correcting for urinary dilution, geometric mean urinary concentrations were higher for the phthalate metabolites MBP, MBzP, mono(3-carboxylpropyl) phthalate, and four metabolites of di(2-ethyl-hexyl) phthalate among women who subsequently delivered preterm. These differences remained, but were somewhat lessened, after correction by specific gravity or creatinine. In multivariate logistic regression analysis adjusted for potential confounders, elevated odds of having phthalate metabolite concentrations above the median level were found.

Conclusions

We found that phthalate exposure is prevalent among this group of pregnant women in Mexico and that some phthalates may be associated with preterm birth.     

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.     

Infectious Disease in a Warming World: How Weather Influenced West Nile Virus in the United States (2001–2005)

Background

The effects of weather on West Nile virus (WNV) mosquito populations in the United States have been widely reported, but few studies assess their overall impact on transmission to humans.

Objectives

We investigated meteorologic conditions associated with reported human WNV cases in the United States.

Methods

We conducted a case–crossover study to assess 16,298 human WNV cases reported to the Centers for Disease Control and Prevention from 2001 to 2005. The primary outcome measures were the incidence rate ratio of disease occurrence associated with mean weekly maximum temperature, cumulative weekly temperature, mean weekly dew point temperature, cumulative weekly precipitation, and the presence of ≥ 1 day of heavy rainfall (≥ 50 mm) during the month prior to symptom onset.

Results

Increasing weekly maximum temperature and weekly cumulative temperature were similarly and significantly associated with a 35–83% higher incidence of reported WNV infection over the next month. An increase in mean weekly dew point temperature was significantly associated with a 9–38% higher incidence over the subsequent 3 weeks. The presence of at least 1 day of heavy rainfall within a week was associated with a 29–66% higher incidence during the same week and over the subsequent 2 weeks. A 20-mm increase in cumulative weekly precipitation was significantly associated with a 4–8% increase in incidence of reported WNV infection over the subsequent 2 weeks.

Conclusions

Warmer temperatures, elevated humidity, and heavy precipitation increased the rate of human WNV infection in the United States independent of season and each others’ effects.     

Effects of Ambient Air Pollution on Hemostasis and Inflammation

Background

Air pollution has consistently been associated with increased morbidity and mortality due to respiratory and cardiovascular disease. Underlying biological mechanisms are not entirely clear, and hemostasis and inflammation are suggested to be involved.

Objectives

Our aim was to study the association of the variation in local concentrations of airborne particulate matter (PM) with aerodynamic diameter < 10 μm, carbon monoxide, nitrogen monoxide, nitrogen dioxide, and ozone with platelet aggregation, thrombin generation, fibrinogen, and C-reactive protein (CRP) levels in healthy individuals.

Methods

From 40 healthy volunteers, we collected 13 consecutive blood samples within a 1-year period and measured light-transmittance platelet aggregometry, thrombin generation, fibrinogen, and CRP. We performed regression analysis using generalized additive models to study the association between the hemostatic and inflammatory variables, and local environmental concentrations of air pollutants for time lags within 24 hr before blood sampling or 24–96 hr before blood sampling.

Results

In general, air pollutants were associated with platelet aggregation [average, +8% per interquartile range (IQR), p < 0.01] and thrombin generation (average, +1% per IQR, p < 0.05). Platelet aggregation was not affected by in vitro incubation of plasma with PM. We observed no relationship between any of the air pollutants and fibrinogen or CRP levels.

Conclusions

Air pollution increased platelet aggregation as well as coagulation activity but had no clear effect on systemic inflammation. These prothrombotic effects may partly explain the relationship between air pollution and the risk of ischemic cardiovascular disease.