Exposure-outcome Relationships Research Articles

Hormonal, liver, and renal function associated with electronic waste (e-waste) exposure in Dhaka, Bangladesh

Electronic waste (e-waste) contains numerous metals and organic pollutants that have detrimental impacts on human health. We studied 199 e-waste recycling workers and 104 non-exposed workers; analyzed blood, urine, and hair samples to measure heavy metals, hormonal, liver, and renal function. We used quantile regression models to evaluate the impact of Pb, Cd, and Hg on hormonal, liver and renal function, and the role of DNA oxidative damage in mediating the relationship between exposures and outcomes. Exposed workers had higher blood lead (Pb) (median 11.89 vs 3.63 µg/dL), similar blood cadmium (Cd) (1.04 vs 0.99 µg/L) and lower total mercury (Hg) in hair (0.38 vs 0.57 ppm) than non-exposed group. Exposed workers also had elevated median concentrations of total triiodothyronine (TT3), aspartate aminotransferase (AST), alanine aminotransferase (ALT), urinary albumin, albumin creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR) were significantly higher than non-exposed group (p≤0.05). Sex hormones including luteinizing hormone, follicle stimulating hormone, estrogen, progesterone and testosterone concentrations were not significantly different between exposed and non-exposed (all p≥0.05). The median concentration of ALT was 4.00 (95% CI: 0.23, 7.77), urinary albumin was 0.09 (95% CI: 0.06, 0.12) and ACR was 1.31 (95% CI: 0.57, 2.05) units higher in the exposed group compared to non-exposed group. Pb was associated with a 3.67 unit increase in the ALP (95% CI: 1.53, 5.80), 0.01 unit increase in urinary albumin (95% CI: 0.002, 0.01), and 0.07 unit increase in ACR (95% CI: 0.01, 0.13). However, no hormonal, renal, and hepatic parameters were associated with Cd or Hg. Oxidative DNA damage did not mediate exposure-outcome relationships (p≥0.05). Our data indicate e-waste exposure impairs liver and renal functions secondary to elevated Pb levels. Continuous monitoring, longitudinal studies to evaluate the dose-response relationship and effective control measure are required to protect workers from e-waste exposure.

Nutrition counselling and clinical outcomes in HIV: A systematic review and meta-analysis.

People living with the HIV (PLHIV) are at an increased risk of various diseases due to a weakened immune system, particularly if they are naïve or poorly adherent to antiretroviral therapy (ART). Nutrients play a critical role in improving immune health, especially among this population. We systematically reviewed the evidence concerning the impact of nutritional counselling on the occurrence of important clinical outcomes among PLHIV. Medical literature databases (PubMed, EMBASE and Web of Science) were searched from inception to October 2022 for relevant published studies (n = 12) of nutritional counselling and HIV-related outcomes in adults on ART. Random-effects meta-analyses were conducted when the exposure-outcome relationships were similar in three or more studies. Although the methodologies of nutritional intervention varied across all studies, overall, the evidence from the meta-analysis indicates a nsignificant positive association between nutrition counselling and improvements in CD4 cell count, body mass index and low-density lipoprotein concentration. However, the existing literature does not provide enough evidence to establish a significant impact of nutrition counselling on other immune, anthropometric, and metabolic outcomes including viral load, weight, and lean mass due to the differences in the study designs. Well-powered randomized controlled trials are needed that explore the effect of evidence-based, individualized nutrition counselling on HIV-related clinical outcomes.

A STRUCTURED APPROACH TO EVALUATING LIFE COURSE INFLUENCES ON DNA METHYLATION AGE ACCELERATION

Abstract Lower socio-economic position (SEP) is associated with increased biological age acceleration measured using DNA methylation (DNAm). Prior studies using cohorts from the US and UK have shown a relationship between social mobility and DNAm age acceleration such that those who experienced upward mobility exhibited slower biological aging relative to continuously advantage groups while those with disadvantaged SEP across the life course experienced the most rapid DNAm age acceleration. However, using a social mobility model, it is not clear to what extent childhood may be a sensitive period for the impact of social disadvantage on DNA methylation or whether an accumulation of disadvantage hypothesis is consistent with the data. In this study, we apply a structured life-course modeling approach (SLCMA), a theory-driven analytical method that compares life course hypotheses of time-dependent exposure-outcome relationships, to determine whether early life is a sensitive period for DNAm modification using data from approximately 4,000 participants of the 2016 Health and Retirement Study (HRS) Venous Blood Study. We hypothesize that childhood is a sensitive period during which exposure to lower socio-economic position results in greater DNAm changes. We compare this to alternative hypotheses including the accumulation of disadvantage, in which the effect of low SEP increases with the duration of exposure, and the recency of disadvantage, in which the effect of low SEP is stronger for exposure in later life.

Statistical Approaches to Study Exposome-Health Associations in the Context of Repeated Exposure Data: A Simulation Study.

The exposome concept aims to consider all environmental stressors simultaneously. The dimension of the data and the correlation that may exist between exposures lead to various statistical challenges. Some methodological studies have provided insight regarding the efficiency of specific modeling approaches in the context of exposome data assessed once for each subject. However, few studies have considered the situation in which environmental exposures are assessed repeatedly. Here, we conduct a simulation study to compare the performance of statistical approaches to assess exposome-health associations in the context of multiple exposure variables. Different scenarios were tested, assuming different types and numbers of exposure-outcome causal relationships. An application study using real data collected within the INMA mother-child cohort (Spain) is also presented. In the simulation experiment, assessed methods showed varying performance across scenarios, making it challenging to recommend a one-size-fits-all strategy. Generally, methods such as sparse partial least-squares and the deletion-substitution-addition algorithm tended to outperform the other tested methods (ExWAS, Elastic-Net, DLNM, or sNPLS). Notably, as the number of true predictors increased, the performance of all methods declined. The absence of a clearly superior approach underscores the additional challenges posed by repeated exposome data, such as the presence of more complex correlation structures and interdependencies between variables, and highlights that careful consideration is essential when selecting the appropriate statistical method. In this regard, we provide recommendations based on the expected scenario. Given the heightened risk of reporting false positive or negative associations when applying these techniques to repeated exposome data, we advise interpreting the results with caution, particularly in compromised contexts such as those with a limited sample size.

The role of total antioxidant capacity and malondialdehyde of seminal plasma in the association between air pollution and sperm quality

Accumulating evidence has suggested that men exposed to air pollution are associated with decreased sperm quality, and seminal plasma plays a pivotal role in maintaining sperm viability. However, the role of seminal plasma in air pollution related sperm quality decline remain unestablished. In current study, we recruited 524 participants from couples who underwent in vitro fertilization treatment due to female factors at a fertility clinic in China from March to August 2020. Conventional sperm parameters, total antioxidant capacity (T-AOC), malondialdehyde (MDA) and testosterone were measured using semen samples. The six main air pollutants (PM2.5, PM10, NO2, SO2, CO, O3) during four key periods of sperm development (meiotic stage, spermiogenesis stage, epididymal stage and total sperm cycle period) were estimated using inverse distance weighting method. Multiple linear regression models were employed to investigate the exposure-outcome relationships. And we found that PM10 exposures were negatively related to sperm total motility and the exposures of PM2.5 and PM10 were inversely associated with sperm progressive motility during epididymal stage. Furthermore, PM2.5 and PM10 exposures were positively associated with seminal plasma MDA and PM10 was negatively related to seminal plasma T-AOC during epididymal stage. PM2.5, PM10 and CO exposures during total sperm cycle period might relate to increased seminal plasma testosterone. Mediation analysis indicated seminal plasma MDA and T-AOC partially mediated PM10 associated reduction of sperm motility during epididymal stage. Our study suggested MDA and T-AOC of seminal plasma played a role in air pollution associated decline of sperm motility.

Improvement of Attention in Subjects Diagnosed with Hyperkinetic Syndrome using BIOVIT Simulator

This study aimed to stimulate the brain's executive function through a series of tasks and rules based on dynamic perceptual stimuli using the Biotechnology Virtual Immersion Simulator (BIOVIT) and thus evaluate its usefulness to maintain and increase attention levels in subjects diagnosed with hyperkinetic syndrome. With a quantitative methodology framed in a longitudinal trend design, the cause of the exposure-outcome relationships was studied using the BIOVIT simulator. Exploratory analysis of oscillatory brain activity was measured using a graphical recording of brain electrical activity and attention levels. Data consisted of 77,566 observations from n = 18 separately studied participants. The findings established that the BIOVIT simulator maintained and increased the attention levels of the participants by 77.8%. Furthermore, the hypothesis was tested that virtual reality immersion technologies significantly affect attention levels in participants aged 8 to 12. The evidence shows that the BIOVIT simulator is an alternative to developing learning methodologies in vulnerable populations. The low implementation costs and the diversity of academic applications may allow schools in developing countries to solve this problem that afflicts thousands of children with attention deficit and hyperactivity disorder

Gaps in Depression Symptom Management for Patients With Head and Neck Cancer.

To understand practice patterns and identify care gaps within a large-scale depression screening program for patients with head and neck cancer (HNC). Retrospective cohort study. This was a population-based study of adults diagnosed with a HNC between January 2007 and October 2020. Each patient was observed from time of first symptom assessment until end of study date, or death. The exposure of interest was a positive depressive symptom screen on the Edmonton Symptom Assessment System (ESAS). Outcomes of interest included psychiatry/psychology assessment, social work referral, or palliative care assessment. Cause specific hazard models with a time-varying exposure were used to investigate the exposure-outcome relationships. Of 14,054 patients with HNC, 9016 (64.2%) reported depressive symptoms on at least one ESAS assessment. Within 60 days of first reporting depressive symptoms, 223 (2.7%) received a psychiatry assessment, 646 (7.9%) a social work referral, and 1131 (13.9%) a palliative care assessment. Rates of psychiatry/psychology assessment (HR 3.15 [95% CI 2.67-3.72]), social work referral (HR 1.83 [95% CI 1.64-2.02]), and palliative care assessment (HR 2.34 [95% CI 2.19-2.50]) were higher for those screening positive for depression. Certain patient populations were less likely to receive an assessment including the elderly, rural residents, and those without a prior psychiatric history. A high proportion of head and neck patients report depressive symptoms, though this triggers a referral in a small number of cases. These data highlight areas for improvement in depression screening care pathways. 3 Laryngoscope, 133:2638-2646, 2023.

Short-term air pollution and temperature exposure and changes in the extracellular microRNA profile of Normative Aging Study (NAS) participants

BackgroundWhile the health effects of air pollution and temperature are widely studied, the molecular effects are poorly understood. Extracellular microRNAs (ex-miRNAs) have the potential to serve as diagnostic or prognostic biomarkers and/or to act as intercellular signaling molecules that mediate the effects of environmental exposures on health outcomes. MethodsWe examined the relationship between short-term exposure to air pollution and ambient temperature and the ex-miRNA profiles of participants in the Normative Aging Study (NAS) from 1999 to 2015. Our exposures were defined as same-day, two-day, three-day, one-week, two-week, and three-week moving averages of PM2.5, NO2, O3, and temperature which were derived from high-resolution spatio-temporal models. The ex-miRNA profiles of the subjects were obtained during follow-up visits. We analyzed the data using a longitudinal quantile regression model adjusted for individual covariates, batch effects, and time trends. We adjusted for multiple comparisons using a false discovery rate (FDR) correction. Ex-miRNAs that were significantly associated with exposures were further investigated using pathway analyses. ResultsWe found that all the examined exposures were associated with changes in ex-miRNA profiles in our study, particularly PM2.5 which was responsible for most of the statistically significant results. We found 110 statistically significant exposure-outcome relationships that revealed associations with the levels of 52 unique ex-miRNAs. Pathway analyses showed these ex-miRNAs have been linked to target mRNAs, genes, and biological mechanisms that could affect virtually every organ system, and as such may be linked to multiple clinical disease presentations such as cardiovascular disease, respiratory disease, and neurological disease. ConclusionsAir pollution and temperature exposures were significantly associated with alterations in the ex-miRNA profiles of NAS subjects with possible biological consequences.

The Use of Urine Biomarker-Creatinine Ratio as the Exposure in Epidemiological Studies Alters the Exposure-Outcome Relationships

The Use of Urine Biomarker-Creatinine Ratio as the Exposure in Epidemiological Studies Alters the Exposure-Outcome Relationships

Fetal exposure to phthalates and bisphenols and DNA methylation at birth: the Generation R Study

BackgroundPhthalates and bisphenols are non-persistent endocrine disrupting chemicals that are ubiquitously present in our environment and may have long-lasting health effects following fetal exposure. A potential mechanism underlying these exposure–outcome relationships is differential DNA methylation. Our objective was to examine the associations of maternal phthalate and bisphenol concentrations during pregnancy with DNA methylation in cord blood using a chemical mixtures approach.MethodsThis study was embedded in a prospective birth cohort study in the Netherlands and included 306 participants. We measured urine phthalates and bisphenols concentrations in the first, second and third trimester. Cord blood DNA methylation in their children was processed using the Illumina Infinium HumanMethylation450 BeadChip using an epigenome-wide association approach. Using quantile g-computation, we examined the association of increasing all mixture components by one quartile with cord blood DNA methylation.ResultsWe did not find evidence for statistically significant associations of a maternal mixture of phthalates and bisphenols during any of the trimesters of pregnancy with DNA methylation in cord blood (all p values > 4.01 * 10–8). However, we identified one suggestive association (p value < 1.0 * 10–6) of the first trimester maternal mixture of phthalates and bisphenols and three suggestive associations of the second trimester maternal mixture of phthalates and bisphenols with DNA methylation in cord blood.ConclusionsAlthough we did not identify genome-wide significant results, we identified some suggestive associations of exposure to a maternal mixture of phthalates and bisphenols in the first and second trimester with DNA methylation in cord blood that need further exploration in larger study samples.

Unintended impacts of the Open Streets program on noise complaints in New York City

Background and Aim: Exposure to high levels of environmental noise and noise annoyance have been associated with detrimental health outcomes. In 2012, a campaign in New York City (NYC) measured noise levels frequently exceeding recommended standards. Noise complaints have been used as a proxy of noise annoyance and exposure. NYC has been opening parts of its street network to recreation and physical activity through the Open Streets program. We aim to describe the citywide distribution of noise complaints by census tract percentage of Open Streets. Methods: We conducted analyses at the census tract level from 2019 to 2021 across NYC. We used noise complaints from 311 calls for specific locations and times, which we aggregated to daily census tract counts of noise complaints. We focused on two categories of noise complaints that may be impacted by Open Streets: vehicle and street/sidewalk noise complaints. We used a mixed-effects model with random intercepts for census tracts to estimate the association between changes in noise complaints and area covered by Open Streets (%) given tract-level socioeconomic status and street geometry. We allowed for nonlinear exposure–outcome relationships using natural splines. We also carried out sensitivity analyses using data from a citizen’s survey on Open Streets implementation levels gathered by Transportation Alternatives (TA) to assess its impact on model results. Results: Census tracts with increasing use of street space as Open Streets (i.e. higher than 5%) reported more daily street/sidewalk noise complaints. For vehicle noise complaints, 5 to 10% of area covered by Open Streets showed increasing noise complaints but estimates plateaued at higher percentages. The sensitivity analyses using TA implementation data showed that our estimates were fairly robust. Conclusions: Our preliminary results suggest that Open Streets were associated with increases in street/sidewalk noise complaints. Keywords (2-6): Policy, Noise annoyance, Open Streets, Urban planning, Cities

Newborn Metabolomic Signatures of Maternal Serum Per- and Polyfluoroalkyl Substance Levels and Reduced Length of Gestation: A Prospective Analysis in the Atlanta African American Maternal-Child Cohort

Background and Aim: Preterm birth (PTB; 22–&amp;#x3c;37 gestational weeks) and early term birth (ETB; 37–38 gestational weeks) disproportionately affect marginalized populations. Exposure to per- and polyfluoroalkyl substances (PFAS) has been reported to reduce length of gestation, but the underlying mechanisms are unknown. Our aim was to characterize the molecular signatures of prenatal PFAS exposure and gestational age at birth outcomes in the newborn dried blood spot (DBS) metabolome. Methods: This prospective cohort study included 267 African American pregnant people who gave birth to a singleton in Atlanta, Georgia between 2016 and 2020. Maternal PFAS concentrations were measured in serum samples obtained between 6–17 gestational weeks. Linear and logistic regression was used to assess associations between PFAS concentrations and gestational weeks at birth or PTB and ETB compared to full-term birth, respectively. Molecular signatures of the exposure-outcome relationships were phenotyped in newborn DBS samples with high-resolution metabolomics. Results: The mean gestational age was 38.7&amp;#xb1;2.0 weeks. Relative to the lowest quartile, the second quartile of serum perfluorooctanoic acid (PFOA) concentration was significantly associated with increased odds of ETB (odds ratio (OR), 2.85; 95% CI 1.16, 7.02) and the second quartile of perfluorohexane sulfonic acid (PFHxS) concentration was significantly associated with medically-indicated PTB or ETB (OR, 6.39; 95% CI 1.20, 34.09) versus healthy full-term birth. After false discovery rate correction, 8 pathways and 52 metabolites were associated with PFAS exposure and gestational age at birth outcomes. Discussion: In this study, pregnant people with higher PFOA and PFHxS concentrations had increased odds of an early birth prior to full-term. The effect of prenatal PFAS exposure on reduced length of gestation was associated with perturbed tissue neogenesis, neuroendocrine function, and redox homeostasis in the newborn DBS metabolome. These mechanisms may be translated into strategies for addressing maternal and child health disparities affecting African Americans.

Bridging differences across cohorts in the relationship between prenatal secondhand smoke exposure and birth weight: Transportability of effect estimates in the ECHO consortium

Background and Aim: Transportability of effect estimates in epidemiology can potentially help investigators explain the differences in effect estimates for the same exposure-outcome relationships observed across different cohorts. In this study we aim to explain potential differences in the relationship between prenatal secondhand smoke exposure (SHS) and birth weight across different cohorts of the Environmental influences on Child Health Outcomes (ECHO) consortium that may be due to population differences in sociodemographic characteristics. Methods: We assessed transportability of effect estimates across 5 different cohorts in the ECHO consortium consisting of 6582 mother-offspring dyads. We first estimated individual cohort effects using Targeted Maximum Likelihood Estimation adjusting for several sociodemographic covariates. We then proceeded to estimate transported effects from one cohort to each of the remaining cohorts using a robust non-parametric estimation approach. We compared the transported effect estimates to the original effect estimates for these cohorts with any decrease in differences between cohort-specific estimates potentially attributable to different sociodemographic variable distributions. Results: Individual cohort effects associated with SHS exposure varied across the 5 cohorts with a range of strongly suggestive results for harmful effects of exposure (149.0 gram decrease in birthweight (95% confidence interval (CI): -254.4, -43.5), to results on the protective side of the null albeit with very wide confidence intervals. Transported effect estimates partially explained differences in 3 out of the 4 cohort pairs, explaining 7% to 97% of the differences in the effect point estimates. Conclusion: Differences in sociodemographic characteristics across different populations may partially explain differences observed in the relationship between prenatal SHS exposure and birth weight across cohorts in the ECHO consortium. This framework could have broader implications in in multi-cohort consortiums by aiding in the comparability of cross-cohort results. Keywords: transportability, causal inference, machine learning, secondhand smoke, birth outcomes

Exploring exposure-outcome relationships inside the VA Normative Aging Study using graph learning

Exploring exposure-outcome relationships inside the VA Normative Aging Study using graph learning

Software Application Profile: SUMnlmr, an R package that facilitates flexible and reproducible non-linear Mendelian randomization analyses

Abstract Motivation Mendelian randomization methods that estimate non-linear exposure-outcome relationships typically require individual-level data. This package implements non-linear Mendelian randomization methods using stratified summarized data, facilitating analyses where individual-level data cannot easily be shared, and additionally increasing reproducibility as summarized data can be reported. Dependence on summarized data means the methods are independent of the form of the individual-level data, increasing flexibility to different outcome types (such as continuous, binary or time-to-event outcomes). Implementation SUMnlmr is available as an R package (version 3.1.0 or higher). General features The package implements the previously proposed fractional polynomial and piecewise linear methods on stratified summarized data that can either be estimated from individual-level data using the package or supplied by a collaborator. It constructs plots to visualize the estimated exposure-outcome relationship, and provides statistics to assess preference for a non-linear model over a linear model. Availability The package is freely available from GitHub [https://github.com/amymariemason/SUMnlmr].

Aetiological research on the health of migrants living in Germany: a systematic literature review

BackgroundGermany has become an important immigration country and health services need to adopt to meet the needs of an increasingly multicultural population. For public health planning, it is essential to...

Association Studies of Environmental Exposures, DNA Methylation and Children's Cognitive, Behavioral, and Mental Health Problems.

Introduction: Prenatal environmental exposures have been associated with children’s cognitive, behavioral, and mental health problems, and alterations in DNA methylation have been hypothesized as an underlying biological mechanism. However, when testing this hypothesis, it is often difficult to overcome the problem of multiple comparisons in statistical testing when evaluating a large number of developmental outcomes and DNA methylation sites as potential mediators. The objective of this study is to implement a ‘meet-in-the-middle’ approach with a sequential roadmap to address this concern. Methods: In the Columbia Center for Children’s Environmental Health birth cohort study, we implemented a 5-step sequential process for identifying CpG sites that mediate associations between prenatal environmental exposures and cognitive, behavioral, and mental health problems as measured by the Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV) and the Child Behavior Checklist (CBCL). These steps include 1) the identification of biological pathways that are relevant to each outcome of interest; 2) selection of a set of genes and CpGs on genes that are significantly associated with the outcomes; 3) identification of exposures that are significantly associated with selected CpGs; 4) examination of exposure-outcome relationships among those where significant CpGs were identified; and 5) mediation analysis of the selected exposures and corresponding outcomes. In this study, we considered a spectrum of environmental exposure classes including environmental phenols, pesticides, phthalates, flame retardants and air pollutants. Results: Among all considered exposures and outcomes, we found one CpG site (cg27510182) on gene (DAB1) that potentially mediates the effect of exposure to PAH on CBCL social problems at children aged 7. Conclusion: This ‘meet-in-the-middle’ approach attenuates concerns regarding multiple comparisons by focusing on genes and pathways that are biologically relevant for the hypothesis.

The associations of prenatal exposure to dioxins and polychlorinated biphenyls with neurodevelopment at 6 Months of age: Multi-pollutant approaches

BackgroundPrenatal exposure to persistent organic pollutants, including polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), dioxin-like polychlorinated biphenyls (DL-PCBs), and nondioxin-like PCBs (NDL-PCBs), has been hypothesized to have a detrimental impact on neurodevelopment. However, the association of prenatal exposure to a dioxin and PCB mixture with neurodevelopment remains largely inconclusive partly because these chemical levels are correlated. ObjectivesWe aimed to elucidate the association of in utero exposure to a mixture of dioxins and PCBs with neurodevelopment measured at 6 months of age by applying multipollutant methods. MethodsA total of 514 pregnant women were recruited between July 2002 and October 2005 in the Sapporo cohort, Hokkaido Study on Environment and Children's Health. The concentrations of individual dioxin and PCB isomers were assessed in maternal peripheral blood during pregnancy. The mental and psychomotor development of the study participants' infants was evaluated using the Bayley Scales of Infant Development-2nd Edition (n = 259). To determine both the joint and individual associations of prenatal exposure to a dioxin and PCB mixture with infant neurodevelopment, Bayesian kernel machine regression (BKMR) and quantile-based g-computation were employed. ResultsSuggestive inverse associations were observed between in utero exposure to a dioxin and PCB mixture and infant psychomotor development in both the BKMR and quantile g-computation models. In contrast, we found no association of a dioxin and PCB mixture with mental development. When group-specific posterior inclusion probabilities were estimated, BKMR suggested prenatal exposure to mono-ortho PCBs as the more important contributing factors to early psychomotor development compared with the other dioxin or PCB groups. No evidence of nonlinear exposure-outcome relationships or interactions among the chemical mixtures was detected. ConclusionsApplying the two complementary statistical methods for chemical mixture analysis, we demonstrated limited evidence of inverse associations of prenatal exposure to dioxins and PCBs with infant psychomotor development.

Health symptom trajectories and neurotoxicant exposures in Gulf War veterans: the Ft. Devens cohort

BackgroundThirty years ago, Gulf War (GW) veterans returned home with numerous health symptoms that have been associated with neurotoxicant exposures experienced during deployment. The health effects from these exposures have been termed toxic wounds. Most GW exposure-outcome studies utilize group analyses and thus individual fluctuations in symptoms may have been masked. This study investigates health symptom trajectories in the same veterans over 25 years.MethodsVeterans were categorized into 5 a priori trajectory groups for each health symptom and Chronic Multisymptom Illness (CMI) clinical case status. Multinomial logistic regression models were used to investigate associations between these trajectories and neurotoxicant exposures.ResultsResults indicate that more than 21 Pyridostigmine Bromide (PB) pill exposure was associated with consistent reporting of fatigue, pain, and cognitive/mood symptoms as well as the development of six additional symptoms over time. Chemical weapons exposure was associated with both consistent reporting and development of neurological symptoms over time. Reported exposure to tent heater exhaust was associated with later development of gastrointestinal and pulmonary symptoms. Veterans reporting exposure to more than 21 PB pills were more than 8 times as likely to consistently meet the criteria for CMI over time.ConclusionThis study highlights the importance of the continued documentation of the health impacts experienced by GW veterans’, their resulting chronic health symptoms, and the importance of exposure-outcome relationships in these veterans now 30 years post-deployment.

Modeling complex effects of exposure to particulate matter and extreme heat during pregnancy on congenital heart defects: A U.S. population-based case-control study in the National Birth Defects Prevention Study

Background/objectiveResearch suggests gestational exposure to particulate matter ≤2.5 μm (PM2.5) and extreme heat may independently increase risk of birth defects. We investigated whether duration of gestational extreme heat exposure modifies associations between PM2.5 exposure and specific congenital heart defects (CHDs). We also explored nonlinear exposure-outcome relationships. MethodsWe identified CHD case children (n = 2824) and non-malformed live-birth control children (n = 4033) from pregnancies ending between 1999 and 2007 in the National Birth Defects Prevention Study, a U.S. population-based multicenter case-control study. We assigned mothers 6-week averages of PM2.5 exposure during the cardiac critical period (postconceptional weeks 3–8) using the closest monitor within 50 km of maternal residence. We assigned a count of extreme heat days (EHDs, days above the 90th percentile of daily maximum temperature for year, season, and weather station) during this period using the closest weather station. Using generalized additive models, we explored logit-nonlinear exposure-outcome relationships, concluding logistic models were reasonable. We estimated joint effects of PM2.5 and EHDs on six CHDs using logistic regression models adjusted for mean dewpoint and maternal age, education, and race/ethnicity. We assessed multiplicative and additive effect modification. ResultsConditional on the highest observed EHD count (15) and at least one critical period day during spring/summer, each 5 μg/m3 increase in average PM2.5 exposure was significantly associated with perimembranous ventricular septal defects (VSDpm; OR: 1.54 [95% CI: 1.01, 2.41]). High EHD counts (8+) in the same population were positively, but non-significantly, associated with both overall septal defects and VSDpm. Null or inverse associations were observed for lower EHD counts. Multiplicative and additive effect modification estimates were consistently positive in all septal models. ConclusionsResults provide limited evidence that duration of extreme heat exposure modifies the PM2.5-septal defects relationship. Future research with enhanced exposure assessment and modeling techniques could clarify these relationships.