ABSTRACT
BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals that persist in the environment and can accumulate in humans, leading to adverse health effects. MicroRNAs (miRNAs) are emerging biomarkers that can advance the understanding of the mechanisms of PFAS effects on human health. However, little is known about the associations between PFAS exposures and miRNA alterations in humans. OBJECTIVE: To investigate associations between PFAS concentrations and miRNA levels in children. METHODS: Data from two distinct cohorts were utilized: 176 participants (average age 17.1 years; 75.6% female) from the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) cohort in the United States, and 64 participants (average age 6.5 years, 39.1% female) from the Rhea study, a mother-child cohort in Greece. PFAS concentrations and miRNA levels were assessed in plasma samples from both studies. Associations between individual PFAS and plasma miRNA levels were examined after adjusting for covariates. Additionally, the cumulative effects of PFAS mixtures were evaluated using an exposure burden score. Ingenuity Pathways Analysis was employed to identify potential disease functions of PFAS-associated miRNAs. RESULTS: Plasma PFAS concentrations were associated with alterations in 475 miRNAs in the Teen-LABs study and 5 miRNAs in the Rhea study (FDR p < 0.1). Specifically, plasma PFAS concentrations were consistently associated with decreased levels of miR-148b-3p and miR-29a-3p in both cohorts. Pathway analysis indicated that PFAS-related miRNAs were linked to numerous chronic disease pathways, including cardiovascular diseases, inflammatory conditions, and carcinogenesis. CONCLUSION: Through miRNA screenings in two independent cohorts, this study identified both known and novel miRNAs associated with PFAS exposure in children. Pathway analysis revealed the involvement of these miRNAs in several cancer and inflammation-related pathways. Further studies are warranted to enhance our understanding of the relationships between PFAS exposure and disease risks, with miRNA emerging as potential biomarkers and/or mediators in these complex pathways.
Subject(s)
Environmental Exposure , Environmental Pollutants , Fluorocarbons , MicroRNAs , Humans , MicroRNAs/blood , Female , Child , Fluorocarbons/blood , Male , Adolescent , Environmental Exposure/adverse effects , Environmental Pollutants/blood , Biomarkers/blood , Cohort Studies , United States , Greece , Longitudinal StudiesABSTRACT
Animal studies have pointed at the liver as a hotspot for per- and polyfluoroalkyl substances (PFAS) accumulation and toxicity; however, these findings have not been replicated in human populations. We measured concentrations of seven PFAS in matched liver and plasma samples collected at the time of bariatric surgery from 64 adolescents in the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) study. Liver:plasma concentration ratios were perfectly explained (r2 > 0.99) in a multilinear regression (MLR) model based on toxicokinetic (TK) descriptors consisting of binding to tissue constituents and membrane permeabilities. Of the seven matched plasma and liver PFAS concentrations compared in this study, the liver:plasma concentration ratio of perfluoroheptanoic acid (PFHpA) was considerably higher than the liver:plasma concentration ratio of other PFAS congeners. Comparing the MLR model with an equilibrium mass balance model (MBM) suggested that complex kinetic transport processes are driving the unexpectedly high liver:plasma concentration ratio of PFHpA. Intratissue MBM modeling pointed to membrane lipids as the tissue constituents that drive the liver accumulation of long-chain, hydrophobic PFAS, whereas albumin binding of hydrophobic PFAS dominated PFAS distribution in plasma. The liver:plasma concentration data set, empirical MLR model, and mechanistic MBM modeling allow the prediction of liver from plasma concentrations measured in human cohort studies. Our study demonstrates that combining biomonitoring data with mechanistic modeling can identify underlying mechanisms of internal distribution and specific target organ toxicity of PFAS in humans.
Subject(s)
Alkanesulfonic Acids , Bariatric Surgery , Environmental Pollutants , Fluorocarbons , Animals , Humans , Adolescent , Cohort Studies , Liver , Fluorocarbons/analysisABSTRACT
BACKGROUND: In environmental epidemiology, measurements of toxicants in biological samples are often used as individual exposure assignments. It is common to obtain only one or a few exposure biomarkers per person and use those measurements to represent each person's relevant toxicant exposure for a given health outcome, even though most exposure biomarkers can fluctuate over time. When the timing of the exposure reflected by the biomarker measurement is misaligned with disease development especially if it occurs after the disease outcome, results could be subject to reverse causality or exposure measurement error. OBJECTIVE: This study aimed to use an approximate Bayesian computation (ABC) method to improve PFOA exposure estimates and characterize the effects of PFOA on preeclampsia in the C8 Studies. METHODS: Serum PFOA concentrations were measured in blood samples collected during 2005-2006 in West Virginia and Ohio (the C8 Studies), and residential and water use histories and pregnancy outcomes were obtained from self-reports. Our previous results may have been influenced by the choice of methods for characterizing PFOA exposures. Here we use an ABC method to combine measured PFOA serum concentrations and environmentally modeled PFOA concentrations to reconstruct historical PFOA exposures. We also expanded our previous work by assuming more realistic lognormal distributions for key input parameters in the exposure and pharmacokinetic models. RESULTS: Compared to using fixed values of model parameters and Monte Carlo simulations, ABC produced similar Spearman correlations between estimated and measured serum PFOA concentrations, yet substantially reduced the mean squared error by over 50%. Based on ABC, compared to previous studies, we found a similar adjusted odds ratio (AOR) for the association between PFOA and preeclampsia. CONCLUSIONS: Bayesian combination of modeled exposure and measured biomarker concentrations can reduce exposure measurement error compared to modeled exposure.
Subject(s)
Fluorocarbons , Pre-Eclampsia , Water Pollutants, Chemical , Bayes Theorem , Caprylates/toxicity , Environmental Exposure/analysis , Female , Fluorocarbons/toxicity , Humans , Pre-Eclampsia/chemically induced , Pre-Eclampsia/epidemiology , Pregnancy , Retrospective StudiesABSTRACT
We conducted a detailed analysis of coronavirus disease in a large population center in southern California, USA (Orange County, population 3.2 million), to determine heterogeneity in risks for infection, test positivity, and death. We used a combination of datasets, including a population-representative seroprevalence survey, to assess the actual burden of disease and testing intensity, test positivity, and mortality. In the first month of the local epidemic (March 2020), case incidence clustered in high-income areas. This pattern quickly shifted, and cases next clustered in much higher rates in the north-central area of the county, which has a lower socioeconomic status. Beginning in April 2020, a concentration of reported cases, test positivity, testing intensity, and seropositivity in a north-central area persisted. At the individual level, several factors (e.g., age, race or ethnicity, and ZIP codes with low educational attainment) strongly affected risk for seropositivity and death.
Subject(s)
COVID-19 , Epidemics , California/epidemiology , Humans , SARS-CoV-2 , Seroepidemiologic StudiesABSTRACT
OBJECTIVES: We conducted serological SARS-CoV-2 antibody testing from October to November 2020 to estimate the SARS-CoV-2 seroprevalence among firefighters/paramedics in Orange County (OC), California. METHODS: OC firefighters employed at the time of the surveillance activity were invited to participate in a voluntary survey that collected demographic, occupational and previous COVID-19 testing data, and a SARS-CoV-2 immunoglobulin (Ig)G antibody blood test. We collected venous blood samples using mobile phlebotomy teams that travelled to individual fire stations, in coordination with an annual tuberculosis testing campaign for firefighters employed by OC Fire Authority (OCFA), and independently for firefighters employed by cities. We estimated seroprevalence and assessed several potential predictors of seropositivity. RESULTS: The seroprevalence was 5.3% among 923 OCFA personnel tested, with 92.2% participating. Among firefighters self-reporting a previous positive COVID-19 antibody or PCR test result, twenty-one (37%) did not have positive IgG tests in the current serosurvey. There were no statistically significant differences in demographic characteristics between cases and non-cases. Work city was a significant predictor of case status (p=0.015). Seroprevalence (4.8%) was similar when aggregated across seven city fire departments (42%-65% participation). In total, 1486°C fire personnel were tested. CONCLUSION: Using a strong serosurvey design and large firefighter cohort, we observed a SARS-CoV-2 IgG seroprevalence of 5.3%. The seroprevalence among OC firefighters in October 2020 was lower than the general county population estimated seroprevalence (11.5%) in August. The difference may be due in part to safety measures taken by OC fire departments at the start of the pandemic, as well as differences in antibody test methods and/or duration of antibody response.
Subject(s)
Antibodies, Viral/immunology , COVID-19/epidemiology , Firefighters/statistics & numerical data , SARS-CoV-2/immunology , Adult , COVID-19/immunology , California/epidemiology , Female , Humans , Immunoglobulin G/immunology , Male , Middle Aged , Occupational Exposure/statistics & numerical data , Seroepidemiologic Studies , Young AdultABSTRACT
BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are ubiquitous in the serum of the general US population. Food, drinking water, consumer products, dust, and air have been assessed as PFAS exposure sources for humans. The effects of various types of carpeting on serum PFAS concentrations have been less studied, despite the known use of PFAS in stain-resistant carpet treatments. OBJECTIVE: This study aimed to examine the associations between serum PFAS concentrations and type of residential flooring among the general US population aged 12 years and older using the 2005-2006 National Health and Nutrition Examination Survey (NHANES). METHODS: We used multiple linear regressions adjusted for complex survey design and relevant covariates to analyze the relations between serum PFAS concentrations and type of floor covering (smooth surface, low pile carpet, medium to high pile carpet, and combination of carpet and smooth surface), as well as other potential exposure factors. We used multiple imputation to address missing values. RESULTS: We found significantly higher serum concentrations of perfluorohexane sulfonic acid (PFHxS) and 2-(N-methyl-perfluorooctane sulfonamido) acetic acid (MeFOSAA) in US residents residing in homes with low pile carpeting compared with those residing in homes with smooth surface. We concluded that among US residents aged 12 years and older residing in homes with low pile carpeting in the home in 2005-2006, on average 24% and 19% of the PFHxS and MeFOSAA body burdens, respectively, could be attributed to carpeting. We found associations between other types of floor covering (medium to high pile carpet, combination of carpet and smooth surface) and some PFAS concentrations compared with the smooth surface, but these results were less consistent and generally not statistically significant. Additionally, a group Wald Chi-squared test showed a significant result for PFOS, indicating different contributions of various types of flooring to PFOS serum concentration. SIGNIFICANCE: Our results are representative of the general US population at the time of the survey, and potentially informative regarding ongoing PFAS exposure from a variety of sources including carpeting.
Subject(s)
Alkanesulfonic Acids , Environmental Pollutants , Fluorocarbons , Caprylates , Child , Floors and Floorcoverings , Humans , Nutrition Surveys , Sulfonic AcidsABSTRACT
Generalized additive models (GAMs) with bivariate smoothers are frequently used to map geographic disease risks in epidemiology studies. A challenge in identifying health disparities has been the lack of intuitive and computationally feasible methods to assess whether the pattern of spatial effects varies over time. In this research, we accommodate time-stratified smoothers into the GAM framework to estimate time-specific spatial risk patterns while borrowing information from confounding effects across time. A backfitting algorithm for model estimation is proposed along with a permutation testing framework for assessing temporal heterogeneity of geospatial risk patterns across two or more time points. Simulation studies show that our proposed permuted mean squared difference (PMSD) test performs well with respect to type I error and power in various settings when compared with existing methods. The proposed model and PMSD test are used geospatial risk patterns of patent ductus arteriosus (PDA) in the state of Massachusetts over 2003-2009. We show that there is variation over time in spatial patterns of PDA risk, adjusting for other known risk factors, suggesting the presence of potential time-varying and space-related risk factors other than the adjusted ones.
Subject(s)
Algorithms , Computer Simulation , HumansABSTRACT
HIV stigma is a harmful social phenomenon present in United States (US)-based health care settings. This study assessed the efficacy of a participatory PhotoVoice-informed stigma reduction training program focusing on people living with HIV (PLWH) and targeting health care workers. Seventy-three (N = 73) participants were assessed at baseline (T1), within approximately a week of the training (T2), and at a 3-month follow-up (T3) regarding their HIV/AIDS knowledge, attitudes towards PLWH, and observations of enacted HIV stigma. Findings indicated that the training increased knowledge and improved attitudes (ß = 0.56, p < 0.01; ß = 0.58, p < 0.01, respectively) at T2, but these effects diminished at T3 (ß = - 0.03, p > 0.05; ß = - 0.29, p > 0.05, respectively). The training did not, however, have an impact on observations of enacted stigma at T2 (ß = 0.10, p > 0.05) or at T3 (ß = 0.02, p > 0.05). Additional participatory stigma reduction programs that involve diverse groups of health care workers, offer salient study incentives, include time-saving training methods, and comprise a variety of stigma measures, may be particularly beneficial.
Subject(s)
Attitude of Health Personnel , HIV Infections/psychology , Health Knowledge, Attitudes, Practice , Health Personnel/education , Social Stigma , Acquired Immunodeficiency Syndrome , Adult , Delivery of Health Care , Female , HIV Infections/diagnosis , Humans , Male , Photography , PrejudiceABSTRACT
AIM: The aim of this study was to determine reference values for oxygen saturation (SpO2 ) in neonates at mild and moderate altitudes. METHODS: Our study included 41 097 consecutively born, asymptomatic neonates from 35 hospitals, located in Yunnan, China, with altitudes ranging from 267 to 2202 m. Pre-and post-ductal SpO2 of each neonate was measured at 24 hours of age and before hospital discharge. All study participants, according to the altitude of birth, were categorised into three groups: low (0-500 m), mild (500-1500 m) and moderate altitude (1500-2500 m). RESULTS: Every 1000-m increase in altitude was associated with a 1.54 per cent decrease in mean SpO2 . The means of pre-ductal SpO2 at low, mild and moderate groups were 97.9%, 96.4% and 95.5%, respectively. We used the 2.5th percentile of SpO2 distribution as the cut-off for neonatal SpO2 screening and defined new cut-off values of ≤93% for mild altitudes, ≤92% for moderate altitudes and no adjustment for low altitudes. CONCLUSION: We recommend revised cut-off values for neonatal SpO2 at mild and moderate altitudes and provide new values for paediatricians to refer to when screening neonates for severe congenital heart or lung diseases.
Subject(s)
Altitude , Oximetry , China , Female , Humans , Infant, Newborn , Oxygen , Pregnancy , Reference ValuesABSTRACT
BACKGROUND: More than 14,000 women in the United States die of ovarian cancer (OC) every year. Disparities in survival have been observed by race and socioeconomic status (SES), and vary spatially even after adjusting for treatment received. This study aimed to determine the impact of geographic location on receiving treatment adherent to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for OC, independent of other predictors. PATIENTS AND METHODS: Women diagnosed with all stages of epithelial OC (1996-2014) were identified through the California Cancer Registry. Generalized additive models, smoothing for residential location, were used to calculate adjusted odds ratios (ORs) and 95% CIs for receiving nonadherent care throughout California. We assessed the impact of distance traveled for care, distance to closest high-quality hospital, race/ethnicity, and SES on receipt of quality care, adjusting for demographic and cancer characteristics and stratifying by disease stage. RESULTS: Of 29,844 patients with OC, 11,419 (38.3%) received guideline-adherent care. ORs for nonadherent care were lower in northern California and higher in Kern and Los Angeles counties. Magnitudes of associations with location varied by stage (OR range, 0.45-2.19). Living farther from a high-quality hospital increased the odds of receiving nonadherent care (OR, 1.18; 95% CI, 1.07-1.29), but travel >32 km to receive care was associated with decreased odds (OR, 0.76; 95% CI, 0.70-0.84). American Indian/other women were more likely to travel greater distances to receive care. Women in the highest SES quintile, those with Medicare insurance, and women of non-Hispanic black race were less likely to travel far. Patients who were Asian/Pacific Islander lived the closest to a high-quality hospital. CONCLUSIONS: Among California women diagnosed with OC, living closer to a high-quality center was associated with receiving adherent care. Non-Hispanic black women were less likely to receive adherent care, and women with lower SES lived farthest from high-quality hospitals. Geographic location in California is an independent predictor of adherence to NCCN Guidelines for OC.
Subject(s)
Healthcare Disparities/standards , Ovarian Neoplasms/epidemiology , Adolescent , Adult , Aged , Female , Geography , Humans , Middle Aged , Retrospective Studies , Young AdultABSTRACT
Temporal trends in plasma concentrations of per- and polyfluoroalkyl substances (PFAS) in free-ranging bottlenose dolphins (Tursiops truncatus) inhabiting two geographic areas: Indian River Lagoon, Florida over the years 2003-2015 and the waters surrounding Charleston, South Carolina over 2003-2013, were examined. Nine PFAS met the inclusion criteria for analysis based on percent of values below level of detection and sampling years. Proportionate percentiles parametric quantile regression assuming lognormal distributions was used to estimate the average ratio of PFAS concentrations per year for each chemical. Plasma concentrations decreased over time for perfluorodecanoate (PFDA), perfluorohexane sulfonate (PFHxS), perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), and perfluoroundecanoate (PFUnDA) in both locations. Perfluorononanoate (PFNA) decreased with time in Indian River Lagoon dolphins. Perfluorododecanoate (PFDoDA) concentrations significantly increased over time among female Indian River Lagoon dolphins. Regulation and phaseout of specific PFAS groups may have led to the decreasing levels of those PFAS and increasing levels of other replacement PFAS.
Subject(s)
Bottle-Nosed Dolphin , Fluorocarbons , Animals , Female , Florida , Rivers , South CarolinaABSTRACT
After publication of the article [1], it was brought to our attention that a number in Table 1 is incorrect.
ABSTRACT
BACKGROUND: Associations between ambient particulate matter < 2.5 µm (PM2.5) and asthma morbidity have been suggested in previous epidemiologic studies but results are inconsistent for areas with lower PM2.5 levels. We estimated the associations between early-life short-term PM2.5 exposure and the risk of asthma or wheeze clinical encounters among Massachusetts children in the innovative Pregnancy to Early Life Longitudinal (PELL) cohort data linkage system. METHODS: We used a semi-bidirectional case-crossover study design with short-term exposure lags for asthma exacerbation using data from the PELL system. Cases included children up to 9 years of age who had a hospitalization, observational stay, or emergency department visit for asthma or wheeze between January 2001 and September 2009 (n = 33,387). Daily PM2.5 concentrations were estimated at a 4-km resolution using satellite remote sensing, land use, and meteorological data. We applied conditional logistic regression models to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CI). We also stratified by potential effect modifiers. RESULTS: The median PM2.5 concentration among participants was 7.8 µg/m3 with an interquartile range of 5.9 µg/m3. Overall, associations between PM2.5 exposure and asthma clinical encounters among children at lags 0, 1 and 2 were close to the null value of OR = 1.0. Evidence of effect modification was observed by birthweight for lags 0, 1 and 2 (p < 0.05), and season of clinical encounter for lags 0 and 1 (p < 0.05). Children with low birthweight (LBW) (< 2500 g) had increased odds of having an asthma clinical encounter due to higher PM2.5 exposure for lag 1 (OR: 1.08 per interquartile range (IQR) increase in PM2.5; 95% CI: 1.01, 1.15). CONCLUSION: Asthma or wheeze exacerbations among LBW children were associated with short-term increases in PM2.5 concentrations at low levels in Massachusetts.
Subject(s)
Air Pollutants/adverse effects , Asthma/epidemiology , Particulate Matter/adverse effects , Respiratory Sounds , Asthma/chemically induced , Child , Child, Preschool , Cross-Over Studies , Environmental Exposure , Female , Humans , Infant , Infant, Newborn , Male , Massachusetts/epidemiology , Particle Size , Prevalence , Respiratory Sounds/etiology , RiskABSTRACT
In toxicology studies hormesis refers to a dose-response relationship with a stimulatory response at low doses and an inhibitory response at high doses. In this manuscript, we particularly focus on a J-shaped dose-response relationship for binary cancer responses. We propose and examine two new flexible models for testing the hypothesis of hormesis in a Bayesian framework. The first model is parametric and enhances the flexibility of modeling a hormetic zone by using a non-linear predictor in a multistage model. The second model is non-parametric and allows multiple model specifications, weighting the contribution of each model via Bayesian model averaging (BMA). Simulation studies show that the non-parametric modeling approach with BMA provides robust sensitivity and specificity for detecting hormesis relative to the parametric approach, regardless of the shape of a hormetic zone.
Subject(s)
Bayes Theorem , Hormesis , Models, Theoretical , Toxicology/methods , HumansABSTRACT
BACKGROUND: Bayesian methods can be used to incorporate external information into epidemiologic exposure-response analyses of silica and lung cancer. METHODS: We used data from a pooled mortality analysis of silica and lung cancer (n = 65,980), using untransformed and log-transformed cumulative exposure. Animal data came from chronic silica inhalation studies using rats. We conducted Bayesian analyses with informative priors based on the animal data and different cross-species extrapolation factors. We also conducted analyses with exposure measurement error corrections in the absence of a gold standard, assuming Berkson-type error that increased with increasing exposure. RESULTS: The pooled animal data exposure-response coefficient was markedly higher (log exposure) or lower (untransformed exposure) than the coefficient for the pooled human data. With 10-fold uncertainty, the animal prior had little effect on results for pooled analyses and only modest effects in some individual studies. One-fold uncertainty produced markedly different results for both pooled and individual studies. Measurement error correction had little effect in pooled analyses using log exposure. Using untransformed exposure, measurement error correction caused a 5% decrease in the exposure-response coefficient for the pooled analysis and marked changes in some individual studies. CONCLUSION: The animal prior had more impact for smaller human studies and for one-fold versus three- or 10-fold uncertainty. Adjustment for Berkson error using Bayesian methods had little effect on the exposure-response coefficient when exposure was log transformed or when the sample size was large. See video abstract at, http://links.lww.com/EDE/B160.
Subject(s)
Inhalation Exposure/statistics & numerical data , Lung Neoplasms/epidemiology , Silicon Dioxide , Animals , Bayes Theorem , Humans , Logistic Models , Lung Neoplasms/mortality , RatsABSTRACT
We recently utilized a suite of environmental fate and transport models and an integrated exposure and pharmacokinetic model to estimate individual perfluorooctanoate (PFOA) serum concentrations, and also assessed the association of those concentrations with preeclampsia for participants in the C8 Health Project (a cross-sectional study of over 69,000 people who were environmentally exposed to PFOA near a major U.S. fluoropolymer production facility located in West Virginia). However, the exposure estimates from this integrated model relied on default values for key independent exposure parameters including water ingestion rates, the serum PFOA half-life, and the volume of distribution for PFOA. The aim of the present study is to assess the impact of inter-individual variability and epistemic uncertainty in these parameters on the exposure estimates and subsequently, the epidemiological association between PFOA exposure and preeclampsia. We used Monte Carlo simulation to propagate inter-individual variability/epistemic uncertainty in the exposure assessment and reanalyzed the epidemiological association. Inter-individual variability in these parameters mildly impacted the serum PFOA concentration predictions (the lowest mean rank correlation between the estimated serum concentrations in our study and the original predicted serum concentrations was 0.95) and there was a negligible impact on the epidemiological association with preeclampsia (no change in the mean adjusted odds ratio (AOR) and the contribution of exposure uncertainty to the total uncertainty including sampling variability was 7%). However, when epistemic uncertainty was added along with the inter-individual variability, serum PFOA concentration predictions and their association with preeclampsia were moderately impacted (the mean AOR of preeclampsia occurrence was reduced from 1.12 to 1.09, and the contribution of exposure uncertainty to the total uncertainty was increased up to 33%). In conclusion, our study shows that the change of the rank exposure among the study participants due to variability and epistemic uncertainty in the independent exposure parameters was large enough to cause a 25% bias towards the null. This suggests that the true AOR of the association between PFOA and preeclampsia in this population might be higher than the originally reported AOR and has more uncertainty than indicated by the originally reported confidence interval.
Subject(s)
Caprylates/blood , Environmental Exposure , Fluorocarbons/blood , Pre-Eclampsia/epidemiology , Water Pollutants, Chemical/blood , Adolescent , Adult , Cross-Sectional Studies , Female , Humans , Odds Ratio , Pre-Eclampsia/chemically induced , Pregnancy , Uncertainty , West Virginia/epidemiology , Young AdultABSTRACT
Many epidemiology studies have investigated associations of perfluorooctanoate (PFOA) exposures with a variety of adverse health outcomes for participants in the C8 Health Project. The exposure concentrations (i.e., air and groundwater) used in these studies were determined primarily based on participant's residential locations. However, for residential addresses that could not be geocoded to the street level, the exposure concentrations were assigned based on population-weighted ZIP code centroid, which may result in exposure mischaracterization. The aim of this current study is to evaluate the potential impact of mischaracterized exposure concentrations due to geocoding uncertainty on the predicted serum PFOA concentrations and the epidemiological association between PFOA exposure and preeclampsia. For both workplace addresses and incompletely geocoded residential addresses, we used Monte Carlo (MC) simulation to assign alternate geographic locations within the reported ZIP code (instead of population-weighted ZIP code centroids) and the corresponding exposure concentrations. We found that mischaracterization of residential exposure due to population-weighted ZIP code centroid assignment had no significant impact on the serum PFOA concentration predictions and the epidemiological association of PFOA exposure with preeclampsia. In contrast, the uncertainty in workplace exposure moderately impacted the rank exposure among the participants. We observed a 41% increase in the average adjusted odds ratio of preeclampsia occurrence that may be due to differing proportions of cases (64.3%) and controls (54.5%) with workplace address geocodes during pregnancy. This finding suggests that differential exposure mischaracterization can be reduced by obtaining accurate exposure information such as street addresses and tap water consumption, for both workplaces and residences. The analysis we present is one approach for estimating the potential impacts of positional errors in a geocoding-based exposure assessment on exposure estimates and epidemiological study results.
Subject(s)
Caprylates/toxicity , Fluorocarbons/toxicity , Geographic Mapping , Pre-Eclampsia/chemically induced , Pre-Eclampsia/epidemiology , Caprylates/blood , Female , Fluorocarbons/blood , Humans , Monte Carlo Method , Ohio/epidemiology , Pregnancy , Uncertainty , West Virginia/epidemiologyABSTRACT
Exposures to particulate matter with diameter of 2.5µm or less (PM2.5) may influence risk of birth defects. We estimated associations between maternal exposure to prenatal traffic-related air pollution and risk of cardiac, orofacial, and neural tube defects among Massachusetts births conceived 2001 through 2008. Our analyses included 2729 cardiac, 255 neural tube, and 729 orofacial defects. We used satellite remote sensing, meteorological and land use data to assess PM2.5 and traffic-related exposures (distance to roads and traffic density) at geocoded birth addresses. We calculated adjusted odds ratios (OR) and confidence intervals (CI) using logistic regression models. Generalized additive models were used to assess spatial patterns of birth defect risk. There were positive but non-significant associations for a 10µg/m(3) increase in PM2.5 and perimembranous ventricular septal defects (OR=1.34, 95% CI: 0.98, 1.83), patent foramen ovale (OR=1.19, 95% CI: 0.92, 1.54) and patent ductus arteriosus (OR=1.20, 95% CI: 0.95, 1.62). There was a non-significant inverse association between PM2.5 and cleft lip with or without palate (OR=0.76, 95% CI: 0.50, 1.10), cleft palate only (OR=0.89, 95% CI: 0.54, 1.46) and neural tube defects (OR=0.77, 95% CI: 0.46, 1.05). Results for traffic related exposure were similar. Only ostium secundum atrial septal defects displayed significant spatial variation after accounting for known risk factors.
Subject(s)
Air Pollutants/toxicity , Heart Defects, Congenital/epidemiology , Maternal Exposure , Mouth Abnormalities/epidemiology , Neural Tube Defects/epidemiology , Particulate Matter/toxicity , Vehicle Emissions/toxicity , Adolescent , Adult , Air Pollution/statistics & numerical data , Environmental Monitoring , Female , Heart Defects, Congenital/chemically induced , Humans , Infant, Newborn , Male , Massachusetts/epidemiology , Mouth Abnormalities/chemically induced , Neural Tube Defects/chemically induced , Particle Size , Particulate Matter/analysis , Spacecraft , Young AdultABSTRACT
BACKGROUND: Charleston Harbor has elevated concentrations of PFAS in dolphins, but local human exposure data are limited. OBJECTIVES: We sought to describe PFAS serum concentrations' temporal trends among Gullah African American residents of coastal South Carolina. METHODS: Longitudinal measures of PFAS in blood serum from a Gullah clinical sample, without lupus, were examined using spaghetti plots and visit-to-visit change scores (e.g., differences in concentrations between visits) among the 68 participants with repeated measures available. We also modeled population-level trends among the 71 participants with any data using proportionate percentile models, accounting for clustering through robust standard errors. In a post-hoc analysis we examined heterogeneity of temporal trends by age through mixed-effects models for the log-transformed PFAS compounds. RESULTS: Population concentrations of PFOS dropped approximately 9 (95% CI: 8, 10) percent each year over 2003-2013. This was concordant with individual PFOS trajectories (median PFOS change score -21.7 ng/g wet weight, interquartile range of PFOS change scores: -32.8, -14.9) and reports for other populations over this time period. Several other compounds including PFOA, PFHxS, and PFuNDA also showed a population-level decrease. However, examination of individual trajectories suggested substantial heterogeneity. Post-hoc analyses indicated that PFAS trajectories were heterogeneous by age. CONCLUSIONS: Many PFAS compounds are decreasing in a sample of Gullah African Americans from coastal South Carolina. There may be age differences in the elimination kinetics of PFASs. The possible role of age as a modifier of PFAS serum trends merits further research.
Subject(s)
Alkanesulfonic Acids/blood , Black or African American , Environmental Exposure/analysis , Environmental Pollutants/blood , Fluorocarbons/blood , Adolescent , Adult , Aged , Aging/blood , Child , Chromatography, High Pressure Liquid , Environmental Exposure/statistics & numerical data , Female , Humans , Longitudinal Studies , Male , Middle Aged , Models, Statistical , South Carolina , Tandem Mass Spectrometry , Young AdultABSTRACT
BACKGROUND: Methylmercury (MeHg), known for well over a century as a neurotoxin in adults, has more recently been studied for potential detrimental effects during early brain development. While several studies have estimated mercury exposure, they usually rely on either a single biomarker or questionnaire data, each of which has limitations. The goal of this paper was to develop a toxicokinetic model that incorporates both biomarker and questionnaire data to estimate the cumulative exposure to MeHg through seafood consumption using data collected from the Childhood Autism Risks from Genetics and the Environment (CHARGE) study. METHODS: We utilized a previously described discrete-time model that estimates blood MeHg concentration given a piecewise-constant ingestion rate and single-compartment pharmacokinetics. We measured newborn bloodspot Hg concentrations and obtained information pertaining to maternal fish consumption using a questionnaire. Using MeHg concentration estimates from the toxicokinetic model, cumulative MeHg exposure was estimated in children with autism, children with developmental delay, and typically developing children. Median estimated cumulative MeHg was compared among diagnostic groups using the Kruskal-Wallis Test. Multinomial logistic regression models were constructed to assess the association between cumulative MeHg concentration and the risk of autism and developmental delay (vs. typical development). RESULTS: The estimated average MeHg concentration of for all fish species consumed by mothers was 42 ppb. Median cumulative MeHg over gestation was similar across diagnostic groups (p-values raged from 0.91 to 0.98). After adjusting for potential confounding, we found no association between cumulative MeHg exposure and the risk of autism (OR = 0.95, 95% CI: 0.95, 1.12) or developmental delay (OR = 1.00, 95% CI: 0.89, 1.13). CONCLUSIONS: The toxicokinetic model described in this paper yielded fish MeHg concentration estimates that are consistent with fish species containing lower levels of MeHg. Overall, cumulative MeHg exposure does not appear to detectably elevate the risk of autism or developmental delay. Based on the regression standard error for the association between ASD and TD, we would have reported statistical significance for an adjusted odds ratio of 1.09 or larger. This method can easily be extended to other epidemiologic studies in which there is a biomarker measurement and questionnaire data regarding exposure.