Search Results (27)

Thyroid hormones (THs) require iodine for biosynthesis and play critical roles in brain development. Perchlorate is an environmental contaminant that reduces serum THs by blocking the uptake of iodine from the blood to the thyroid gland. Using a pregnant rodent model, we examined the impact of maternal exposure to perchlorate under conditions of dietary iodine deficiency (ID) on the brain and behavior of offspring. We observed modest reductions in thyroxine (T4) in the serum of dams and no effect on T4 in pup serum in response to maternal exposure to 300 ppm of perchlorate in the drinking water. Likewise, serum T4 was reduced in ID dams, but, as with perchlorate, no effects were evident in the pup. However, when ID was coupled with perchlorate, reductions in pup serum THs and transcriptional alterations in the thyroid gland and pup brain were detected. These observations were accompanied by reductions in the number of cortical inhibitory interneurons containing the calcium-binding protein parvalbumin (Pvalb). Alterations in Pvalb expression in the neonatal brain were associated with deficits in the prepulse inhibition of acoustic startle in adult male offspring and enhanced fear conditioning in females. These findings support and extend structural defects in the brain previously reported in this model. Further, they underscore the critical need to consider additional non-chemical stressors in the determination of hazards and risks posed by environmental contaminants that affect the thyroid system. Full article

The primary aim of this prospective study was to examine the single and combined effect of prenatal exposure to perceived stress, probable depression, and lead on toddlers’ neurodevelopment using the Bayley Scales of Infant and Toddler Development, third edition. Data from 363 mother-toddler pairs enrolled in the Caribbean Consortium for Research in Environmental and Occupational Health prospective cohort study were analyzed. A prenatal lead exposure of ≥3.5 µg/dL was associated with significantly lower receptive (p = 0.008) and expressive (p = 0.006) communication scaled scores. Moderate and severe maternal prenatal probable depression scores were associated with significantly lower fine (p = 0.009) and gross (p = 0.009) motor scaled scores. However, a maternal report of prenatal stress was not associated with neurodevelopmental outcomes. After adjusting for maternal demographics, prenatal stress and lead exposure, prenatal probable depression remained predictive of the toddlers’ gross motor scaled scores (β −0.13, 95% CI [−0.24–−0.02]). Similarly, when adjusting for demographics, prenatal stress and probable depression, prenatal lead exposure remained a significant predictor of their receptive communication scaled scores (β −0.26, 95% CI [−0.49–−0.02]). An analysis testing combined exposure to perceived stress, probable depression, and lead exposure, measured using a cumulative risk index, significantly predicted the child fine motor scaled scores after adjusting for other covariates (β −0.74, 95% CI: [−1.41–−0.01]). Full article

Columbus, Ohio is one of the more prosperous, well-educated, and progressive cities in the United States. However, it ranks as the second worst life expectancy at birth, has a census tract wealth gap (27-year disparity), and one of the higher infant mortality rates in the country. These data suggest that there are likely several high-risk, vulnerable neighborhoods in Columbus with residents experiencing disparate and adverse outcomes. Illustrative of this fact are studies that have examined the social processes and mechanisms through which neighborhood contexts are at the forefront, including exposures to chemical stressors such as particulate matter (PM_2.5) as well as non-chemical stressors including violence, social determinants of health, zoning, and land use policies. It is documented that disparate and adverse outcomes are magnified in the vulnerable neighborhoods on the Near East Side as compared to Columbus city proper, Franklin County and/or the state of Ohio. As such, we developed a nuanced community engagement framework to identify potential environmental hazards associated with adverse pregnancy outcomes in those census tracts. The refined framework uses a blended version of traditional community-based participatory research (CBPR) models and is referred to as E⁶, Enhancing Environmental Endeavors via e-Equity, Education, and Empowerment. Full article

During the 2015–2016 Zika Virus (ZIKV) epidemic in Brazil, the geographical distributions of ZIKV infection and microcephaly outbreaks did not align. This raised doubts about the virus as the single cause of the microcephaly outbreak and led to research hypotheses of alternative explanatory factors, such as environmental variables and factors, agrochemical use, or immunizations. We investigated context and the intermediate and structural determinants of health inequalities, as well as social environment factors, to determine their interaction with ZIKV-positive- and ZIKV-negative-related microcephaly. The results revealed the identification of 382 associations among 382 nonredundant variables of Zika surveillance, including multiple determinants of environmental public health factors and variables obtained from 5565 municipalities in Brazil. This study compared those factors and variables directly associated with microcephaly incidence positive to ZIKV and those associated with microcephaly incidence negative to ZIKV, respectively, and mapped them in case and control subnetworks. The subnetworks of factors and variables associated with low birth weight and birthweight where birth incidence served as an additional control were also mapped. Non-significant differences in factors and variables were observed, as were weights of associations between microcephaly incidence, both positive and negative to ZIKV, which revealed diagnostic inaccuracies that translated to the underestimation of the scope of the ZIKV outbreak. A detailed analysis of the patterns of association does not support a finding that vaccinations contributed to microcephaly, but it does raise concerns about the use of agrochemicals as a potential factor in the observed neurotoxicity arising from the presence of heavy metals in the environment and microcephaly not associated with ZIKV. Summary: A comparative network inferential analysis of the patterns of variables and factors associated with Zika virus infections in Brazil during 2015–2016 coinciding with a microcephaly epidemic identified multiple contributing determinants. This study advances our understanding of the cumulative interactive effects of exposures to chemical and non-chemical stressors in the built, natural, physical, and social environments on adverse pregnancy and health outcomes in vulnerable populations. Full article

Humans are exposed to a diverse mixture of chemical and non-chemical exposures across their lifetimes. Well-designed epidemiology studies as well as sophisticated exposure science and related technologies enable the investigation of the health impacts of mixtures. While existing statistical methods can address the most basic questions related to the association between environmental mixtures and health endpoints, there were gaps in our ability to learn from mixtures data in several common epidemiologic scenarios, including high correlation among health and exposure measures in space and/or time, the presence of missing observations, the violation of important modeling assumptions, and the presence of computational challenges incurred by current implementations. To address these and other challenges, NIEHS initiated the Powering Research through Innovative methods for Mixtures in Epidemiology (PRIME) program, to support work on the development and expansion of statistical methods for mixtures. Six independent projects supported by PRIME have been highly productive but their methods have not yet been described collectively in a way that would inform application. We review 37 new methods from PRIME projects and summarize the work across previously published research questions, to inform methods selection and increase awareness of these new methods. We highlight important statistical advancements considering data science strategies, exposure-response estimation, timing of exposures, epidemiological methods, the incorporation of toxicity/chemical information, spatiotemporal data, risk assessment, and model performance, efficiency, and interpretation. Importantly, we link to software to encourage application and testing on other datasets. This review can enable more informed analyses of environmental mixtures. We stress training for early career scientists as well as innovation in statistical methodology as an ongoing need. Ultimately, we direct efforts to the common goal of reducing harmful exposures to improve public health. Full article

The cumulative exposure to chemical and non-chemical stressors may have an impact on birth outcomes. The aim of this study is to examine the cumulative exposure of a mixture of chemicals (mercury, lead, selenium and tin) and non-chemical stressors (social support, perceived stress, probable depression and BMI) on birth outcomes (birthweight, gestational age at birth, and Apgar score at 5 min). The study population is a subset (n = 384) of the Caribbean Consortium for Research in Environmental and Occupational Health–MeKiTamara prospective cohort study. Associations between the latent chemical construct, non-chemical stressors and birth outcomes were assessed using path models. The results showed a significant direct relationship between perceived stress and birthweight (β = −0.17), however even though the relationship between perceived stress and depression was significant in all three path models (β = 0.61), the association between depression and birth outcomes was not significant. Perceived stress was significantly associated with community engagement (β = −0.12) and individual resilience (β = −0.12). BMI (β = 0.12) was also significantly directly associated with birthweight. The latent chemical construct did not show an association with the birth outcomes. Our data indicate the need for the development of a support system for pregnant women by involving them in prenatal care programs to reduce maternal stress, which may also influence depression and (in)directly improve the birth outcomes. Interventions regarding weight management for women of childbearing age are necessary to halt obesity and its negative effects on birth outcomes. Full article

Prenatal maternal exposure to air pollution may cause adverse health effects in offspring, potentially through altered immune responses. Maternal psychosocial distress can also alter immune function and may increase gestational vulnerability to air pollution exposure. We investigated whether prenatal exposure to air pollution is associated with altered immune responses in cord blood mononuclear cells (CBMCs) and potential modification by maternal depression in 463 women recruited in early pregnancy (1999–2001) into the Project Viva longitudinal cohort. We estimated black carbon (BC), fine particulate matter (PM_2.5), residential proximity to major roadways, and near-residence traffic density, averaged over pregnancy. Women reported depressive symptoms in mid-pregnancy (Edinburgh Postnatal Depression Scale) and depression history by questionnaire. Immune responses were assayed by concentrations of three cytokines (IL-6, IL-10, and TNF-α), in unstimulated or stimulated (phytohemagglutinin (PHA), cockroach extract (Bla g 2), house dust mite extract (Der f 1)) CBMCs. Using multivariable linear or Tobit regression analyses, we found that CBMCs production of IL-6, TNF-a, and IL-10 were all lower in mothers exposed to higher levels of PM_2.5 during pregnancy. A suggestive but not statistically significant pattern of lower cord blood cytokine concentrations from ever (versus never) depressed women exposed to PM_2.5, BC, or traffic was also observed and warrants further study. Full article

Increasing numbers of chemicals are on the market and present in consumer products. Emerging evidence on the relationship between environmental contributions and prevalent diseases suggests associations between early-life exposure to manufactured chemicals and a wide range of children’s health outcomes. Using current assessment methodologies, public health and chemical management decisionmakers face challenges in evaluating and anticipating the potential impacts of exposure to chemicals on children’s health in the broader context of their physical (built and natural) and social environments. Here, we consider a systems approach to address the complexity of children’s environmental health and the role of exposure to chemicals during early life, in the context of nonchemical stressors, on health outcomes. By advancing the tools for integrating this more complex information, the scope of considerations that support chemical management decisions can be extended to include holistic impacts on children’s health. Full article

General cognitive ability, often referred to as ‘general intelligence’, comprises a variety of correlated abilities. Childhood general cognitive ability is a well-studied area of research and can be used to predict social outcomes and perceived success. Early life stage (e.g., prenatal, postnatal, toddler) exposures to stressors (i.e., chemical and non-chemical stressors from the total (built, natural, social) environment) can impact the development of childhood cognitive ability. Building from our systematic scoping review (Ruiz et al., 2016), we conducted a meta-analysis to evaluate more than 100 stressors related to cognitive development. Our meta-analysis identified 23 stressors with a significant increase in their likelihood to influence childhood cognitive ability by 10% or more, and 80 stressors were observed to have a statistically significant effect on cognitive ability. Stressors most impactful to cognition during the prenatal period were related to maternal health and the mother’s ability to access information relevant to a healthy pregnancy (e.g., diet, lifestyle). Stressors most impactful to cognition during the early childhood period were dietary nutrients (infancy), quality of social interaction (toddler), and exposure to toxic substances (throughout early childhood). In conducting this analysis, we examined the relative impact of real-world exposures on cognitive development to attempt to understand the inter-relationships between exposures to both chemical and non-chemical stressors and early developmental life stages. Our findings suggest that the stressors observed to be the most influential to childhood cognitive ability are not permanent and can be broadly categorized as activities/behaviors which can be modified to improve childhood cognition. This meta-analysis supports the idea that there are complex relationships between a child’s total environment and early cognitive development. Full article

Interdisciplinary approaches are needed to measure the additive or multiplicative impacts of chemical and non-chemical stressors on child development outcomes. The lack of interdisciplinary approaches to environmental health and child development has led to a gap in the development of effective intervention strategies. It is hypothesized that a broader systems approach can support more effective interventions over time. To achieve these goals, detailed study protocols are needed. Researchers in child development typically focus on psychosocial stressors. Less attention is paid to chemical and non-chemical stressors and how the interaction of these stressors may impact child development. This feasibility study aims to bridge the gap between child development and environmental epidemiology research by trialing novel methods of gathering ultrafine particle data with a wearable air sensor, while simultaneously gathering language and noise data with the Language Environment Analysis (LENA) system. Additionally, psychosocial data (e.g., parenting quality, caregiver depression, and household chaos) was gathered from parent reports. Child participants (age 3–4 years) completed cognitive tasks to assess self-regulation and receptive language skills, and provided a biospecimen analyzed for inflammatory biomarkers. Data collection was completed at two time points, roughly corresponding to fall and spring. Twenty-six participants were recruited for baseline data, and 11 participants completed a follow-up session. Preliminary results indicate that it is feasible to gather personal Particulate Matter (PM2.5), language, and noise data, cognitive assessments, and biospecimens from our sample of 3-4-year-old children. While there are obstacles to overcome when working with this age group, future studies can benefit from adapting lessons learned regarding recruitment strategies, study design, and protocol implementation. Full article

Prenatal exposure to mercury, stress, and depression may have adverse effects on birth outcomes. Little is known on the influence of chemical and non-chemical stressors on birth outcomes in the country of Suriname. We assessed the influence of prenatal exposure to mercury, perceived stress, and depression on adverse birth outcomes in 1143 pregnant Surinamese women who participated in the Caribbean Consortium for Research in Environmental and Occupational Health-MeKiTamara prospective cohort study. Associations between mercury (≥1.1 μg/g hair, USEPA action level/top versus bottom quartile), probable depression (Edinburgh Depression Scale ≥12), high perceived stress (Cohen’s Perceived Stress Scale ≥20), and adverse birth outcomes (low birthweight (<2500 g), preterm birth (<37 completed weeks of gestation), and low Apgar score (<7 at 5 min)) were assessed using bivariate and multivariate logistic regressions. Prevalence of elevated mercury levels, high perceived stress, and probable depression were 37.5%, 27.2%, and 22.4%, respectively. Mercury exposure was significantly associated with preterm birth in the overall study cohort (OR 2.47; 95% CI 1.05–5.83) and perceived stress with a low Apgar score (OR 9.73; 95% CI 2.03–46.70). Depression was not associated with any birth outcomes. These findings can inform policy- and practice-oriented solutions to improve maternal and child health in Suriname. Full article

Childhood behavioral outcomes have been linked to low quality intrauterine environments caused by prenatal exposures to both chemical and non-chemical stressors. The effect(s) from the many stressors a child can be prenatally exposed to may be influenced by complex interactive relationships that are just beginning to be understood. Chemical stressors influence behavioral outcomes by affecting the monoamine oxidase A (MAOA) enzyme, which is involved in serotonin metabolism and the neuroendocrine response to stress. Non-chemical stressors, particularly those associated with violence, have been shown to influence and exacerbate the externalizing behavioral outcomes associated with low MAOA activity and slowed serotonin metabolism. The adverse developmental effects associated with high stress and maternal drug use during pregnancy are well documented. However, research examining the combined effects of other non-chemical and chemical stressors on development and childhood outcomes as a result of gestational exposures is scarce but is an expanding field. In this systematic review, we examined the extant literature to explore the interrelationships between exposures to chemical and non-chemical stressors (specifically stressful/traumatic experiences), MAOA characteristics, and childhood externalizing behaviors. We observed that exposures to chemical stressors (recreational drugs and environmental chemicals) are significantly related to externalizing behavioral outcomes in children. We also observed that existing literature examining the interactions between MAOA characteristics, exposures to chemical stressors, and traumatic experiences and their effects on behavioral outcomes is sparse. We propose that maternal stress and cortisol fluctuations during pregnancy may be an avenue to link these concepts. We recommend that future studies investigating childhood behaviors include chemical and non-chemical stressors as well as children’s inherent genetic characteristics to gain a holistic understanding of the relationship between prenatal exposures and childhood behavioral outcomes. Full article

Background: Children are exposed to chemical and non-chemical stressors from their built, natural, and social environments. Research is needed to advance our scientific understanding of non-chemical stressors, evaluate how they alter the biological response to a chemical stressor, and determine how they impact children’s health and well-being. To do this, we conducted a state-of-the-science review of non-chemical stressors found in a child’s social environment. Methods: Studies eligible for inclusion in this review were identified through a search of the peer-reviewed literature using PubMed and PsycINFO. Combinations of words associated with non-chemical stressors and children were used to form search strings. Filters were used to limit the search to studies published in peer-reviewed journals from 2000–2016 and written in English. Publications found using the search strings and filters went through two rounds of screening. Results: A total of 146 studies met the inclusion criteria. From these studies, 245 non-chemical stressors were evaluated. The non-chemical stressors were then organized into 13 general topic areas: acculturation, adverse childhood experiences, economic, education, family dynamics, food, greenspace, neighborhood, social, stress, urbanicity, violence, and other. Additional information on health outcomes, studies evaluating both chemical and non-chemical stressors, and animal studies are provided. This review provides evidence that non-chemical stressors found in a child’s social environment do influence their health and well-being in both beneficial (e.g., salutatory effects of greenspace and social support) and adverse (e.g., poor relationships between health and selected non-chemical stressors such as economics, educational attainment, exposure to violence, stress) ways. Conclusions: This literature review identified a paucity of studies addressing the combined effects of chemical and non-chemical stressors and children’s health and well-being. This literature review was further complicated by inconsistencies in terminology, methodologies, and the value of non-chemical stressor research in different scientific disciplines. Despite these limitations, this review showed the importance of considering non-chemical stressors from a child’s social environment when addressing children’s environmental health considerations. Full article

Metals, stress, and sociodemographics are commonly studied separately for their effects on birth outcomes, yet often jointly contribute to adverse outcomes. This study analyzes two methods for measuring cumulative risk to understand how maternal chemical and nonchemical stressors may contribute to small for gestational age (SGA). SGA was calculated using sex-specific fetal growth curves for infants of pregnant mothers (n = 2562) enrolled in the National Institute of Child Health and Human Development (NICHD) Fetal Growth Study. The exposures (maternal lead, mercury, cadmium, Cohen’s perceived stress, Edinburgh depression scores, race/ethnicity, income, and education) were grouped into three domains: metals, psychosocial stress, and sociodemographics. In Method 1 we created cumulative risk scores using tertiles. Method 2 employed weighted quantile sum (WQS) regression. For each method, logistic models were built with three exposure domains individually and race/ethnicity, adjusting for age, parity, pregnancy weight gain, and marital status. The adjusted effect of overall cumulative risk with three domains, was also modeled using each method. Sociodemographics was the only exposure associated with SGA in unadjusted models ((odds ratio) OR: 1.35, 95% (confidence interval) CI: 1.08, 1.68). The three cumulative variables in adjusted models were not significant individually, but the overall index was associated with SGA (OR: 1.17, 95% CI: 1.02, 1.35). In the WQS model, only the sociodemographics domain was significantly associated with SGA. Sociodemographics tended to be the strongest risk factor for SGA in both risk score and WQS models. Full article

Cumulative risk assessment (CRA) has been proposed as a means of evaluating possible additive and synergistic effects of multiple chemical, physical and social stressors on human health, with the goal of informing policy and decision-making, and protecting public health. Routine application of CRA to environmental regulatory and policy decision making, however, has been limited due to a perceived lack of appropriate quantitative approaches for assessing combined effects of chemical and nonchemical exposures. Seven research projects, which represented a variety of disciplines, including population health science, laboratory science, social sciences, geography, statistics and mathematics, were funded by the US Environmental Protection Agency (EPA) to help address this knowledge gap. We synthesize key insights from these unique studies to determine the implications for CRA practice and priorities for further research. Our analyses of these seven projects demonstrate that the necessary analytical methods to support CRA are available but are ultimately context-dependent. These projects collectively provided advancements for CRA in the areas of community engagement, characterization of exposures to nonchemical stressors, and assessment of health effects associated with joint exposures to chemical and psychosocial stressors. Full article