Polychlorinated biphenyls and incident coronary heart disease-related outcomes in Great Lakes fish consumers.

BACKGROUND: Exposure to polychlorinated biphenyls (PCBs) has been linked to risk factors for cardiovascular disease such as increased inflammation, accelerated atherosclerosis, diabetes, and sex hormone dysregulation. Furthermore, there is increasing evidence suggesting associations between internal dose of PCBs and cardiovascular outcomes. OBJECTIVES: The purpose of this study is to investigate longitudinal associations of PCBs with coronary heart disease (CHD)-related outcomes in a cohort of Great Lakes sport fish consumers. METHODS: The Great Lakes Sport Fish Consumer cohort was established in the early 1990's. Eight hundred nineteen participants were followed from 1993 to 2017. Serum PCBs were measured in 1994/1995 (baseline), in 2001, and in 2004, while health history questionnaires were administered in 1996, 2003, 2010, and 2017. Cox models were used to prospectively investigate associations of total PCBs and PCB groupings, based on aryl hydrocarbon receptor activity, with incident self-reported physician diagnosis of coronary heart disease (CHD), myocardial infarction (MI), and angina pectoris. RESULTS: A 2-fold increase in phenobarbital-type PCBs was associated with a 72% increase in likelihood of self-reported incident diagnosis of CHD (HR=1.72, 95% CI: 1.06-2.81; p=0.0294). Similar results were observed for total PCBs (HR=1.68, 95% CI: 1.05-2.69; p=0.0306) and mixed methacholine/phenobarbital type (mixed-type) PCBs (HR=1.60, 95% CI: 1.02-2.52; p=0.0427), but not methacholine-type PCBs. PCBs were not strongly associated with risk of MI or angina. CONCLUSIONS: This study presents evidence that exposure to PCBs increases the risk of developing coronary heart disease. Given the large number of risk factors and causal pathways for CHD, future research is required to better understand biological mechanisms of action for PCBs on CHD.

Associations between Novel and Legacy Per- and Polyfluoroalkyl Substances in Human Serum and Thyroid Cancer: A Case and Healthy Population in Shandong Province, East China.

Per- and polyfluoroalkyl substances (PFASs) are widely detected in the environment and may cause adverse human health effects after exposure. Studies on the effect of PFASs on some health end points, including cancer, are still limited and show inconsistent results. In this research, 319 participants were recruited from Shandong Province, East China, consisting of patients with thyroid cancer and healthy controls. Seven novel and legacy PFASs were frequently detected (detection rate > 75%) in the serum samples of the participants. The concentrations of perfluorooctanoic acid (PFOA) were the highest in the case and control groups. Males showed significantly higher concentrations of PFASs than females. Exposure to PFASs was inversely associated with the risk of thyroid cancer. In the control group, we identified significant positive associations between PFASs and free thyroxine (FT4) as well as between PFOA and thyroid stimulating hormone (TSH) in females. A significant negative association between perfluorononanoic acid (PFNA) and triiodothyronine (T3) was observed in males. Our results suggest that exposure to certain PFASs could interfere with thyroid function. To our knowledge, this is the first case-control study demonstrating associations between novel and legacy PFASs in human and thyroid cancer.

Associations of exposure to metal and metal mixtures with thyroid hormones: Results from the NHANES 2007-2012.

BACKGROUND: Disrupted thyroid homeostasis plays a role in neurocognitive dysfunction and metabolic disorders. Since individuals are exposed to multiple metals simultaneously, it is important to assess the effects of metal mixtures on thyroid hormone status. This study aimed to investigate the associations of metal mixtures and individual metals with thyroid hormone levels. METHODS: Data included 2399 men and 1988 women from the 2007-2012 National Health and Nutrition Examination Survey (2007-2012). Thyroid hormones measured included total triiodothyronine (T3), total thyroxine (T4), free forms of T3 (FT3) and T4 (FT4), and thyroid stimulating hormone (TSH). We included twelve metals (arsenic, barium, cobalt, cesium, molybdenum, antimony, thallium, tungsten, and uranium from urine; cadmium, lead, and mercury from blood) in traditional linear regression models controlling for 12 metals simultaneously and in quantile-based g-computation (QGC) to assess the relative contribution of each metal as well as the overall association with thyroid hormones as a metal mixture. RESULTS: There were associations of the total metal mixture with thyroid hormones for T3 (beta: -0.023, 95% CI: -0.04, -0.01, in women), T4 (beta: -0.03, 95% CI: -0.05, -0.01, in men; beta: -0.026, 95% CI: -0.04, -0.01, in women), and the T3:T4 ratio (beta: 0.026, 95% CI: 0.01, 0.05, in men). Arsenic had negative contributions to T3 and T4. Cadmium had a positive contribution to T4 but negative contributions to T3 and T3:T4. Lead had a positive contribution to T3 and T3:T4, but a negative contribution to T4. CONCLUSION: Multiple metals as a mixture were associated with thyroid hormone levels. Arsenic, cadmium, and lead were individually associated with multiple thyroid hormones. Examination of associations of metal mixtures and individual metals with thyroid hormones can contribute to an understanding of thyroid hormone homeostasis and provide evidence for developing intervention and guidance for health promotion.

Exposure to organochlorine pesticides and the risk of type 2 diabetes in the population of East China.

Organochlorine pesticides (OCPs) have been reported to be associated with an elevated risk of type 2 diabetes, although no study has focused on such associations in Chinese populations. In this case-control study, we aimed to explore the associations between OCPs and type 2 diabetes and their potential mechanisms in a population from East China. Participants diagnosed with type 2 diabetes and nondiabetic participants from Shandong Province, East China, were enrolled in this case-control study. Six OCPs (ß-HCH, trans-chlordane, trans-nonachlor, p,p'-DDE, p,p'-DDT and mirex/kepone) were detected in more than 75% of serum samples. Logistic regression analysis and multiple linear regression analysis were used to assess the associations between OCP exposure and the outcomes. After adjusting for potential confounding factors such as age, sex and body mass index, all six OCPs showed positive associations with type 2 diabetes in a linear dose-response manner. Serum concentrations of ß-HCH and p,p'-DDE were associated with higher levels of fasting plasma glucose in participants without diabetes, although no OCPs showed significant associations with hemoglobin A1c. In addition, certain OCPs showed significantly positive associations with triglycerides, total cholesterol, and low-density lipoprotein cholesterol and negative relationships with high-density lipoprotein cholesterol in nondiabetics, indicating that OCP exposure may disrupt lipid metabolism. Findings in the current study indicated that OCPs may be a diabetogenic factor in the population of this study. To our knowledge, this is the first study to investigate the associations between OCP exposure and type 2 diabetes in a Chinese population.

Associations between Exposure to Persistent Organic Pollutants and Thyroid Function in a Case-Control Study of East China.

Animal studies have indicated that persistent organic pollutants (POPs) affect thyroid hormone homeostasis, while epidemiological studies involving human have not shown consistent results. In this study, we investigated the associations between POP exposure and thyroid function among adult population of East China. One hundred eighty-six participants diagnosed with thyroid disease and 186 participants without thyroid disease from Shandong, China were enrolled in the case-control study during 2016 to 2017. We found that POP exposure was significantly and positively associated with the risk of thyroid disease. The association of thyroid disease with a sum of 17 POPs followed a nonmonotonic dose response, with an adjusted odds ratio of 2.09 (95% confidence intervals: 1.13-3.87, p = 0.019) for the second quartile. Among 186 participants in the control group, concentrations of POPs showed negative associations with triiodothyronine (T3), free T3 (FT3), thyroxine (T4), and free T4 (FT4) in males and positive associations with T4 and FT4 in females. Taken together, these findings suggest that POP exposure can disrupt thyroid hormone homeostasis and increase the risk of thyroid disease.

Associations between blood cadmium concentration and kidney function in the U.S. population: Impact of sex, diabetes and hypertension.

BACKGROUND: Exposure to cadmium has been associated with nephropathy and implicated in the development of diabetes and hypertension. The role of environmental metal exposure may be an underexplored risk factor for decreased kidney function among people with diabetes and/or hypertension. The objective of this study was to examine the association of blood concentration of cadmium with kidney function parameters and evaluate sex, diabetes, and hypertension as effect modifiers of the association. METHODS: This study used data from 12,577 adult participants in the National Health and Nutrition Examination Survey (NHANES) 2007-2012 cycles. We used multivariable linear and logistic regression models to conduct a cross-sectional analysis of the association between cadmium exposure quartiles and estimated glomerular filtration rate (eGFR), urine albumin to creatinine ratio (UACR), low eGFR (defined as eGFR <60 mL/minute/1.73 m2), and albuminuria (defined as UACR ≥ 30 mg/g). Models were adjusted for confounders and interaction terms were evaluated for cadmium concentration and sex, diabetes, and hypertension. Final models were stratified by sex and indices of existing diabetes and hypertension status. RESULTS: The mean eGFR was 94.3 mL/minute/1.73 m2 (SD 21.5) and the geometric mean of UACR was 7.9 mg/g (95% CI 7.6-8.2 mg/g). Blood cadmium concentration was inversely associated with eGFR and positively associated with UACR. We found significant effect modification of the association of eGFR with cadmium, predominantly for sex and hypertension. The strength of the association between cadmium quartiles and eGFR was more pronounced among females compared to males. Among females with hypertension and diabetes, eGFR was lower on average by 4.9 mL/minute/1.73 m2 (95% CI -10.1 to 0.29) in the highest versus lowest cadmium quartile, and in females with hypertension alone, eGFR was lower on average by 5.8 mL/minute/1.73 m2 (95% CI -8.2 to -3.3) in the highest versus lowest cadmium quartile. Among those in the highest exposure quartile, higher mean UACR was observed among participants with hypertension compared to those without. CONCLUSIONS: Our results confirm that cadmium exposure is associated with decreased glomerular filtration and increased urine protein excretion, and provide evidence that the magnitude of these associations differ by sex and may vary based on preexisting diabetes and hypertension. Future prospective sex-specific investigations are necessary to address concerns of reverse causality and efforts should be made to reduce smoking and environmental contamination from cadmium to protect human health.

Urinary arsenic concentration, airway inflammation, and lung function in the U.S. adult population.

BACKGROUND: Inorganic arsenic (iAs) is ubiquitous in the environment and has been linked to lung cancer and a number of non-malignant lung disease in both adults and children. However, most studies were conducted in populations with higher arsenic exposure levels in drinking water and relatively little epidemiologic research evaluated the impacts of low levels iAs exposure on non-malignant lung disease among populations that are not primarily exposed to arsenic through drinking water. OBJECTIVES: We assessed the associations of arsenic exposure with airway inflammation and lung function among U.S. adults aged 20-79 years using data from the National Health and Nutrition Examination Survey 2007-2012 cycles. METHODS: Two measures of arsenic exposure, urinary total arsenic and dimethylarsonic acid (DMA), were used. We calibrated these two exposure measures by regressing their concentrations by arsenobetaine and extracting the residuals to calculate estimated total arsenic and estimated DMA. Arsenic exposures were modeled as log-transformed continuous variables as well as quartile categories. Fractional exhaled nitric oxide (FENO), an indicator of respiratory inflammation, was available for participants. For lung function, the best forced expiratory volume in the first one second (FEV1), forced vital capacity (FVC), forced expiratory flow rate (FEF) 25-75%, their percent estimated values, ratios of FEV1 to FVC, and FEF 25-75% to FVC were used (i.e. FEV1/FVC and FEF/FVC). Weighted multivariable linear regression models, adjusted for potential confounders, were used to evaluate the association of arsenic exposure with airway inflammation and lung function overall, and among males and females. RESULTS: Significant associations between arsenic exposure and increased airway inflammation were found. A two-fold increase in urinary total arsenic and DMA was associated with 23.87% (95% CI: 2.66, 49.46) and 14.05% (95% CI: 1.77, 27.81) higher levels of FENO, respectively. In addition, participants in the highest quartile of urinary total arsenic had FENO levels 8.49% (95% CI: 1.13, 16.39) higher than those in the lowest quartile. These associations were similar between males and females. Limited evidence was found for the association with respect to lung function and potential modification effect of sex. CONCLUSIONS: Arsenic exposure was related to increased risk of airway inflammation but there is limited evidence of an association in relation to lung function. Future research conducted in populations with relatively lower exposure levels that are not primarily exposed to arsenic through drinking water is needed to confirm our findings.

Prenatal exposure to nitrate in drinking water and the risk of congenital anomalies.

BACKGROUND: Nitrate is a common water contaminant that has been associated with birth defects, although the evidence is limited. The purpose of this study was to examine whether maternal consumption of nitrate through drinking water is associated with an increased risk of congenital anomalies. METHODS: The study included a total of 348,250 singletons births from the state of Missouri between January 1, 2004 and December 31, 2008. Individual-level birth defect data and maternal and child characteristics were obtained from the Missouri birth defects registry and state vital statistics records. Outcomes were linked with county-specific monthly estimates of the nitrate concentration in finished water, based on data collected for compliance with the Safe Drinking Water Standard. Poisson models were fit to examine the association between nitrate exposure and birth defects. Average nitrate exposure during the first trimester and over 12 months prior to birth were modeled as continuous variables. Sensitivity analyses included restriction of the sample to counties with <20% and <10% private well usage to reduce exposure misclassification as well as limiting the analyses to residents of rural counties only to account for potential confounding by urbanicity. RESULTS: Estimated water concentrations of nitrate were generally low and below the Environmental Protection Agency's maximum contaminant level of 10 mg/L. Nitrate exposure was associated with a significantly increased risk of limb deficiencies (RR for 1 mg/L (RR1) = 1.26, 95% CI = 1.05, 1.51) in models without well restriction. Nitrate was also weakly associated with an increased risk of congenital heart defects (RR1 = 1.13, 95%CI = 0.93, 1.51) and neural tube defects (RR1 = 1.18, 95%CI = 0.93, 1.51) in models with well restriction (<10%). CONCLUSION: The positive associations found between nitrate exposure via drinking water and congenital abnormalities are largely consistent with some previous epidemiologic studies. The results of this study should be interpreted with caution given limitations in our ability to estimate exposures and the lack information on some risk factors for congenital abnormalities. Our findings may have serious policy implications given that exposure levels in our study were well below current EPA standards for nitrate in drinking water.

The impact on T-regulatory cell related immune responses in rural women exposed to polycyclic aromatic hydrocarbons (PAHs) in household air pollution in Gansu, China: A pilot investigation.

Previous studies found associations between impairments of immune functions and exposure to polycyclic aromatic hydrocarbons (PAHs) in ambient air pollution in the U. S. and China. However, the results remain inconclusive due to the limitations of these studies. In this study, we aimed to examine the direction and magnitude of immune changes related to PAH exposure from household air pollution among rural women living in Gansu, China. Healthy village women (n = 34) were recruited and enrolled in the study. Questionnaires were administered. Blood and urine samples were collected and analyzed during non-heating (September 2017, "summer") and heating (January 2018, "winter") seasons. Urinary 1-hydroxypyrene (1-OHP) was quantified as the biomarker of PAH exposure. To evaluate Treg cell related immune functions, we examined immunoglobulin E (IgE), percent of T-regulatory (Treg) cells, and gene expression of following: forkhead box transcription factor 3 (Foxp3), transforming growth factor-ß (TGF-ß), interleukin 10 (IL-10), and interleukin 35 (IL-35), composed of interleukin-12 alpha (IL-12α) and Epstein-Barr-virus-induced gene 3 (EBi3). Urinary 8-hydroxy-2-deoxyguanosine (8-OHdG) was measured to evaluate oxidative DNA damage. The results showed that the concentration of 1-OHP increased from 0.90 to 17.4 µmol mol-Cr -1 from summer to winter (p < 0.001). Meanwhile, average percent of Treg cells decreased from 5.01% to 1.15% (p < 0.001); IgE and mRNA expressions of Foxp3, TGF-ß, IL-10, IL-12α and EBi3 all significantly decreased (p < 0.001); Urinary 8-OHdG increased from 12.7 to 30.3 ng mg-Cr -1 (p < 0.001). The changes in 8-OHdG, Foxp3 and TGF-ß were significantly associated with the increase of 1-OHP. The results suggested that we observed a substantial increase of PAH exposure in winter, which was significantly associated with the repression on Treg cell function and oxidative DNA damage. Exposure to PAHs in household air pollution possibly induced immune impairments among rural women in northwest China.

Association of methylmercury intake from seafood consumption and blood mercury level among the Asian and Non-Asian populations in the United States.

BACKGROUND: MeHg is a well-established neurotoxicant for fetal brain growth and development and has been shown to increase the risk of cardiovascular disease in aging populations. In the U.S., Asian populations are of particular concern because of their seafood consumption behaviors. OBJECTIVES: Our objective was to calculate the average daily MeHg intake (ADMI) from seafood and to assess the relationship between ADMI with blood methylmercury (BMeHg) concentrations, specifically among women of reproductive age (WORA) and adults ≥ 50 years of age. METHODS: We estimated ADMI from seafood using the 30-day fish consumption data from the NHANES 2011-2014 datasets. Using multivariable linear regression, we estimated the proportional change in mean BMeHg associated with a doubling of the ADMI. Further, correlations between ADMI and BMeHg were compared between Asians and other racial/ethnic groups. RESULTS: Our analysis found both Asian WORA and Asian adults age ≥ 50 years old had significantly higher BMeHg levels and ADMI than their Non-Asian counterparts. Correlations between ADMI from seafood and blood Hg levels were stronger among Asian WORA than among Non-Asian WORA. Key fish species that influenced the dietary MeHg intake for Asians were mackerel, tuna, and "other known/unknown fish species". CONCLUSION: We confirmed that Asian populations have higher MeHg intake than the Non-Asian population in the U.S. and seafood intake is a key predictor of blood Hg concentration, especially among Asian women of reproductive age. Future studies should incorporate information on other known and unknown fish species that are frequently consumed by Asian populations and different parts and fish organs eaten to better understand determinants of MeHg exposure.

Atrazine and nitrate in drinking water and the risk of preterm delivery and low birth weight in four Midwestern states.

BACKGROUND: Atrazine and nitrate are common contaminants in water, and there is limited evidence that they are associated with adverse birth outcomes. The objective of this study was to examine whether atrazine and nitrate in water are associated with an increased risk of preterm delivery (PTD) and term low birth weight (LBW). METHODS: The study included a total of 134,258 singletons births born between January 1, 2004 and December 31, 2008 from 46 counties in four Midwestern states with public water systems that were included in the U.S. Environmental Protection Agency (EPA)'s atrazine monitoring program (AMP). Counties with a population of >300,000 were eliminated from the analyses in order to avoid confounding by urbanicity. Monthly child's sex, race and Hispanic ethnicity specific data were obtained from the states for estimating rates of PTD (<37 weeks) and very preterm (VPTD, <32 weeks), term LBW (<2.5kg among infants born at term) and very low birth weight (VLBW, <1.5kg). The rates were linked with county specific monthly estimates of the concentration of atrazine and nitrate in finished water. Multivariable negative binomial models were fitted to examine the association between the exposures and the adverse birth outcomes. Models were fitted with varying restrictions on the percentage of private well usage in the counties in order to limit the degree of exposure misclassification. RESULTS: Estimated water concentrations of atrazine (mean=0.42 ppb) and nitrate (mean=0.95ppm) were generally low. Neither contaminant was associated with an increased risk of term LBW. Atrazine exposure was associated with a significant increased rate of PTD when well use was restricted to 10% and the exposure was averaged over 4-6 months prior to birth (Rate Ratio for 1ppm increase [RR1ppm]=1.08, 95%CI=1.05,1.11) or over 9 months prior to birth (RR1ppm=1.10, 95%CI=1.01,1.20). Atrazine exposure was also associated with an increased rate of VPTD when when well use was restricted to 10% and the exposure was averaged over 7-9 months prior to birth (RR1ppm=1.19, 95%CI=1.04,1.36). Exposure to nitrate was significantly associated with an increased rate of VPTD (RR1ppm=1.08, 95%CI=1.02,1.15) and VLBW (RR1ppm=1.17, 95%CI=1.08,1.25) when well use was restricted to 20% and the exposure was averaged over 9 months prior to birth. CONCLUSION: The positive and negative findings from our study need to be interpreted cautiously given its ecologic design, and limitations in the data for the exposures and other risk factors. Nonetheless, our findings do raise concerns about the potential adverse effects of these common water contaminants on human development and health, and the adequacy of current regulatory standards. Further studies of these issues are needed with individual level outcome data and more refined estimates of exposure.

Arsenic in drinking water and adverse birth outcomes in Ohio.

BACKGROUND: Arsenic in drinking water has been associated with adverse reproductive outcomes in areas with high levels of naturally occurring arsenic. Less is known about the reproductive effects of arsenic at lower levels. OBJECTIVES: This research examined the association between low-level arsenic in drinking water and small for gestational age (SGA), term low birth weight (term LBW), very low birth weight (VLBW), preterm birth (PTB), and very preterm birth (VPTB) in the state of Ohio. METHODS: Exposure was defined as the mean annual arsenic concentration in drinking water in each county in Ohio from 2006 to 2008 using Safe Drinking Water Information System data. Birth outcomes were ascertained from the birth certificate records of 428,804 births in Ohio from the same time period. Multivariable generalized estimating equation logistic regression models were used to assess the relationship between arsenic and each birth outcome separately. Sensitivity analyses were performed to examine the roles of private well use and prenatal care utilization in these associations. RESULTS: Arsenic in drinking water was associated with increased odds of VLBW (AOR 1.14 per µg/L increase; 95% CI 1.04, 1.24) and PTB (AOR 1.10; 95% CI 1.06, 1.15) among singleton births in counties where <10% of the population used private wells. No significant association was observed between arsenic and SGA, or VPTB, but a suggestive association was observed between arsenic and term LBW. CONCLUSIONS: Arsenic in drinking water was positively associated with VLBW and PTB in a population where nearly all (>99%) of the population was exposed under the current maximum contaminant level of 10µg/L. Current regulatory standards may not be protective against reproductive effects of prenatal exposure to arsenic.

Perfluoroalkyl substances and fish consumption.

BACKGROUND: Perfluoroalkyl substances (PFAS) are an emerging class of contaminants. Certain PFAS are regulated or voluntarily limited due to concern about environmental persistence and adverse health effects, including thyroid disease and dyslipidemia. The major source of PFAS exposure in the general population is thought to be consumption of seafood. OBJECTIVES: In this analysis we examine PFAS levels and their determinants, as well as associations between PFAS levels and self-reported fish and shellfish consumption, using a representative sample of the U.S. METHODS: Data on PFAS levels and self-reported fish consumption over the past 30 days were collected from the 2007-2008, 2009-2010, 2011-2012, and 2013-2014 cycles of the National Health and Nutrition Examination Survey. Twelve different PFAS were measured in serum samples from participants. Ordinary least squares regression models were used to identify factors (demographic characteristics and fish consumption habits) associated with serum PFAS concentrations. Additional models were further adjusted for other potential exposures including military service and consumption of ready-to-eat and fast foods. RESULTS: Seven PFAS were detected in at least 30% of participants and were examined in subsequent analyses (PFDA, PFOA, PFOS, PFHxS, MPAH, PFNA, PFUA). The PFAS with the highest concentrations were PFOS, followed by PFOA, PFHxS and PFNA (medians of 8.3, 2.7, 1.5 and 1.0ng/mL). Fish consumption was generally low, with a median of 1.2 fish meals and 0.14 shellfish meals, reported over the past 30 days. After adjusting for demographic characteristics, total fish consumption was associated with reduced MPAH, and with elevated PFDE, PFNA and PFuDA. Shellfish consumption was associated with elevations of all PFAS examined except MPAH. Certain specific fish and shellfish types were also associated with specific PFAS. Adjustment for additional exposure variables resulted in little to no change in effect estimates for seafood variables. CONCLUSIONS: PFAS are emerging contaminants with widespread exposure, persistence, and potential for adverse health effects. In the general population, fish and shellfish consumption are associated with PFAS levels, which may indicate an avenue for education and outreach.

Livestock and poultry density and childhood cancer incidence in nine states in the USA.

BACKGROUND: Parental occupational and childhood exposures to farm animals have been positively associated with childhood brain tumors, whereas associations with childhood leukemia are equivocal. The developing immune system may be influenced by allergen, virus, or other exposures from animal sources, which may contribute to childhood cancer incidence. METHODS: Incident cancers (acute lymphoblastic leukemia [ALL], acute myeloid leukemia [AML], central nervous system [CNS], peripheral nervous system [PNS]) for children aged 0-4 diagnosed between 2003 and 2008 were obtained from nine National Cancer Institute Surveillance, Epidemiology and End Results (SEER) registries and were linked to U.S. Census of Agriculture data from 2002 and 2007 by county of diagnosis. Animal densities (animal units [AU]/km2; one animal unit is 1000 pounds of animal weight) were estimated for hogs, cattle, chickens (layers and broilers, separately), equine (horses, ponies, mules, burros, donkeys), goats, sheep, turkeys, and total animals. Animal density was examined in models as both continuous (AU per km2) and categorical variables (quartiles). Animal operation densities (per km2) by size of operation (cattle, hogs, chickens, sheep) were modeled continuously. Rate ratios and 95% confidence intervals were estimated using Poisson regression. RESULTS: We found positive associations between AML and broiler chicken densities (RRper 10AU/km2 = 1.14, 95% CI = 1.02-1.26). ALL rates increased with densities of hog operations (RRper operation/100km2 = 1.06, 95% CI = 1.02-1.11). PNS cancer rates were inversely associated with layer chicken density (RRper log of AU/km2 = 0.94, 95% CI = 0.89-0.99). No association was found between any cancer type and densities of cattle, equine, or goats. CONCLUSIONS: Although limited by the ecologic study design, some of our findings are novel and should be examined in epidemiological studies with individual level data.

Arsenic in drinking water and prostate cancer in Illinois counties: An ecologic study.

BACKGROUND: Inorganic arsenic is a lung, bladder, and skin carcinogen. One of the major sources of exposure to arsenic is through naturally contaminated drinking water. While positive associations have been observed between arsenic in drinking water and prostate cancer, few studies have explored this association in the United States. OBJECTIVES: To evaluate the association between inorganic arsenic concentrations in community water systems and prostate cancer incidence in Illinois using an ecologic study design. METHODS: Illinois Environmental Protection Agency data on arsenic concentrations in drinking water from community water systems throughout the state were linked with county-level prostate cancer incidence data from 2007 to 2011 from the Illinois State Cancer Registry. Incidence rates were indirectly standardized by age to calculate standardized incidence ratios (SIRs) for each county. A Poisson regression model was used to model the association between county-level SIRs and mean arsenic tertile (0.33-0.72, 0.73-1.60, and 1.61-16.23ppb), adjusting for potential confounders. RESULTS: For counties with mean arsenic levels in the second tertile, the SIR was 1.05 (95% CI: 0.96-1.16). For counties with mean arsenic levels in the third tertile, the SIR was 1.10 (95% CI: 1.03-1.19). There was a significant linear dose-response relationship observed between mean arsenic levels and prostate cancer incidence (p for trend=0.003). CONCLUSIONS: In this ecologic study, counties with higher mean arsenic levels in community water systems had significantly higher prostate cancer incidence. Individual-level studies of prostate cancer incidence and low-level arsenic exposure are needed.

Water recreation and illness severity.

The health endpoint of prior studies of water recreation has been the occurrence of gastrointestinal (GI) illness. This dichotomous measure fails to take into account the range of symptom severity among those with GI illness, and those who develop GI symptoms but who do not satisfy the definition of GI illness. Data from two US cohort studies were used to assess use of ordinal and semi-continuous measures of GI symptoms, such as duration of GI symptoms and responses to those symptoms such as medication use, interference with daily activities, and utilization of healthcare service. Zero-inflated negative binomial and logistic regression models were used to assess associations between severity and either the degree of water exposure or water quality. Among 37,404 water recreators without baseline GI symptoms, we observed individuals with relatively low severity satisfying the case definition of GI illness, while others with high severity not satisfying that definition. Severity metrics were associated with water exposure. The dichotomous GI illness outcome could be improved by considering symptom severity in future studies. Modeling ordinal and semi-continuous outcomes may improve our understanding of determinants of the burden of illness rather than simply the number of cases of illness attributable to environmental exposures.

Diabetes Screening in US Women With a History of Gestational Diabetes, National Health and Nutrition Examination Survey, 2007-2012.

INTRODUCTION: Women with a history of gestational diabetes mellitus (GDM) are at increased risk for developing type 2 diabetes mellitus. We examined individual, socioeconomic, and health care use characteristics of women with a history of GDM and the association of those characteristics with diabetes screening, and we estimated their rates of undiagnosed prediabetes and diabetes. METHODS: Using 3 cycles of the National Health and Nutrition Examination Survey (2007-2008, 2009-2010, and 2011-2012), we identified 284 women with a history of GDM who were eligible for diabetes screening. Screening status was defined by self-report of having had a blood test for diabetes within the prior 3 years. Undiagnosed prediabetes and diabetes were assessed by hemoglobin A1c measurement. RESULTS: Among women with a history of GDM, 67% reported diabetes screening within the prior 3 years. Weighted bivariate analyses showed screened women differed from unscreened women in measured body mass index (BMI) category (P = .01) and number of health visits in the prior year (P = .001). In multivariable analysis, screening was associated with a greater number of health visits in the prior year (1 visit vs 0 visits, adjusted odds ratio [AOR], 1.91; 95% confidence interval [CI], 0.71-5.18; 2 or 3 visits, AOR, 7.05; and ≥4 visits, AOR, 5.83). Overall, 24.4% (95% CI, 18.3%-31.7%) of women had undiagnosed prediabetes and 6.5% (95% CI, 3.7%-11.3%) had undiagnosed diabetes. CONCLUSION: More health visits in the prior year was associated with receiving diabetes screening. Fewer opportunities for screening may delay early detection, clinical management, and prevention of diabetes. Prediabetes in women with a history of GDM may be underrecognized and inadequately treated.

Associations between bone mineral density and urinary phthalate metabolites among post-menopausal women: a cross-sectional study of NHANES data 2005-2010.

Bone mineral density (BMD) decreases with age, especially among post-menopausal women. Exposures to endocrine disruptors, such as phthalate diesters, could alter BMD through a variety of unidentified mechanisms. A hypothesis-generating study investigated associations between urinary phthalate metabolites and BMD at the femoral neck and spine in post-menopausal women (n = 480) participating in the National Health and Nutrition Examination Survey, from 2005 to 2010. Mono-ethyl phthalate (MEP), molar sum of low molecular weight metabolites (mono-n-butyl phthalate (MNBP), mono-isobutyl phthalate (MIBP), MEP), molar sum of estrogenic metabolites (MNBP, MIBP, MEP, mono-benzyl phthalate (MBZP)), and an estrogenic equivalency factor were negatively associated with spinal BMD. Some associations were modified by age or BMI. The cross-sectional study design, uncertainty regarding the critical time window of exposure, the potential for exposure misclassification, and residual confounding limit our abilities to draw causal conclusions regarding phthalate metabolites and BMD in post-menopausal women. Future studies should address these limitations.

Relationship between in utero C-reactive protein levels and asthma in at-risk children.

BACKGROUND: Asthma research has focused on postnatal exposures, but there is recent evidence to indicate atopic immune responses might be initiated in utero. Systemic inflammation during pregnancy might indicate an environment that could increase propensity in the child to develop allergic disease. OBJECTIVE: To investigate the association of systemic inflammation, as measured by C-reactive protein (CRP) levels, with asthma and wheezing in offspring within an at-risk, mostly Mexican, cohort. METHODS: Using data from a randomized education intervention of families at risk for asthma from 1998 followed through 2009 in urban Chicago, asthma was defined as ever having a physician diagnosis of asthma by 3 years of age and wheezing before the third year. Logistic regression models controlling for confounders investigated the effect of prenatal CRP levels on these outcomes. RESULTS: There were 244 mother-child pairs included in the study analysis with median prenatal CRP levels of 4.9 mg/L (interquartile range 3.2-7.7). Continuous prenatal CRP levels were predictive of asthma by year 3 (relative risk 2.4, 95% confidence interval 1.3, 3.6) and wheezing in year 3 (relative risk 1.7, 95% confidence interval 1.1, 2.4) after adjustment. Associations remained significant in mothers who were of Mexican ethnicity and were nonsmokers, suggesting that effects might be stronger in children at lower risk of disease. CONCLUSION: Prenatal CRP levels are associated with asthma by year 3 and wheezing in year 3 within a high-risk, urban, mostly Mexican, cohort. Maternal systemic inflammation might reflect a prenatal environment that could increase offspring susceptibility to develop wheezing and asthma young in life.

Methyl mercury exposure in populations at risk: Analysis of NHANES 2011-2012.

BACKGROUND: Ingestion of fish contaminated with methyl mercury can lead to adverse health outcomes, particularly when exposure occurs in utero. NHANES 2011-2012 includes total blood mercury (TBHg) and methyl mercury (MeHg) measurements as well as a unique race/ethnicity category for Asians, allowing for improved analysis of determinants of risk. OBJECTIVE: Our objective was to characterize the current burden of MeHg exposure in the US among subgroups who are at risk of health effects due to their physiologic vulnerability to MeHg's effects and/or due to frequent fish consumption, specifically women of childbearing age (WCBA) and adults ≥50 years of age. METHODS: We calculated 90th and 95th percentile estimates as well as geometric means of MeHg for predictive variables. We used multivariable linear regression analyses to estimate the proportional change in mean MeHg associated with each category of all predictive variables. We calculated the validity of screening procedures using fish consumption questions and TBHg testing to predict elevated MeHg. RESULTS: The geometric mean MeHg levels were highest among Asian WCBA (1.17 µg/L) and Asians ≥50 years old (2.49 µg/L). Over 23% of Asian WCBA had levels ≥3.5 µg/L and 25% of Asians ≥50 years old had levels ≥5.8 µg/L. Frequency of fish consumption explained 21-23% of the variation in MeHg. Twenty-five percent of women eating fish ≥ twice per week had MeHg ≥3.5 µg/L. TBHg showed high validity for MeHg ≥5.8 µg/L, and two-step screening using ≥2 fish meals/month followed by TBHg also showed high validity. CONCLUSION: Asian WCBA continue to have increased MeHg exposure from fish consumption, putting their offspring at risk. Screening for MeHg among high-risk groups should be considered.