An Umbrella Review of Meta-Analyses Evaluating Associations between Human Health and Exposure to Major Classes of Plastic-Associated Chemicals.
Background: Epidemiological research investigating the impact of exposure to plastics, and plastic-associated chemicals, on human health is critical, especially given exponentially increasing plastic production. In parallel with increasing production, academic research has also increased exponentially both in terms of the primary literature and ensuing systematic reviews with meta-analysis. However, there are few overviews that capture a broad range of chemical classes to present a state of play regarding impacts on human health. Methods: We undertook an umbrella review to review the systematic reviews with meta-analyses. Given the complex composition of plastic and the large number of identified plastic-associated chemicals, it was not possible to capture all chemicals that may be present in, and migrate from, plastic materials. We therefore focussed on a defined set of key exposures related to plastics. These were microplastics, due to their ubiquity and potential for human exposure, and the polymers that form the matrix of consumer plastics. We also included plasticisers and flame retardants as the two classes of functional additive with the highest concentration ranges in plastic. In addition, we included bisphenols and per- and polyfluoroalkyl substances (PFAS) as two other major plastic-associated chemicals with significant known exposure through food contact materials. Epistemonikos and PubMed were searched for systematic reviews with meta-analyses, meta-analyses, and pooled analyses evaluating the association of plastic polymers, particles (microplastics) or any of the selected groups of high-volume plastic-associated chemicals above, measured directly in human biospecimens, with human health outcomes. Results: Fifty-two systematic reviews were included, with data contributing 759 meta-analyses. Most meta-analyses (78%) were from reviews of moderate methodological quality. Across all the publications retrieved, only a limited number of plastic-associated chemicals within each of the groups searched had been evaluated in relevant meta-analyses, and there were no meta-analyses evaluating polymers, nor microplastics. Synthesised estimates of the effects of plastic-associated chemical exposure were identified for the following health outcome categories in humans: birth, child and adult reproductive, endocrine, child neurodevelopment, nutritional, circulatory, respiratory, skin-related and cancers. Bisphenol A (BPA) is associated with decreased anoclitoral distance in infants, type 2 diabetes (T2D) in adults, insulin resistance in children and adults, polycystic ovary syndrome, obesity and hypertension in children and adults and cardiovascular disease (CVD); other bisphenols have not been evaluated. Phthalates, the only plasticisers identified, are associated with spontaneous pregnancy loss, decreased anogenital distance in boys, insulin resistance in children and adults, with additional associations between certain phthalates and decreased birth weight, T2D in adults, precocious puberty in girls, reduced sperm quality, endometriosis, adverse cognitive development and intelligence quotient (IQ) loss, adverse fine motor and psychomotor development and elevated blood pressure in children and asthma in children and adults. Polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) but not other flame retardants, and some PFAS were identified and are all associated with decreased birth weight. In general populations, PCBs are associated with T2D in adults and endometriosis, bronchitis in infants, CVD, non-Hodgkin's lymphoma (NHL) and breast cancer. In PCB-poisoned populations, exposure is associated with overall mortality, mortality from hepatic disease (men), CVD (men and women) and several cancers. PBDEs are adversely associated with children's cognitive development and IQ loss. PBDEs and certain PFAS are associated with changes in thyroid function. PFAS exposure is associated with increased body mass index (BMI) and overweight in children, attention deficit hyperactive disorder (ADHD) in girls and allergic rhinitis. Potential protective associations were found, namely abnormal pubertal timing in boys being less common with higher phthalate exposure, increased high-density lipoprotein (HDL) with exposure to mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) and reduced incidence of chronic lymphocytic lymphoma (a subtype of NHL) with PCB exposure. Conclusions: Exposure to plastic-associated chemicals is associated with adverse outcomes across a wide range of human health domains, and every plastic-associated chemical group is associated with at least one adverse health outcome. Large gaps remain for many plastic-associated chemicals. Recommendations: For research, we recommend that efforts are harmonised globally to pool resources and extend beyond the chemicals included in this umbrella review. Priorities for primary research, with ensuing systematic reviews, could include micro- and nanoplastics as well as emerging plastic-associated chemicals of concern such as bisphenol analogues and replacement plasticisers and flame retardants. With respect to chemical regulation, we propose that safety for plastic-associated chemicals in humans cannot be assumed at market entry. We therefore recommend that improved independent, systematic hazard testing for all plastic-associated chemicals is undertaken before market release of products. In addition because of the limitations of laboratory-based testing for predicting harm from plastic in humans, independent and systematic post-market bio-monitoring and epidemiological studies are essential to detect potential unforeseen harms.
Symeonides C
,Aromataris E
,Mulders Y
,Dizon J
,Stern C
,Barker TH
,Whitehorn A
,Pollock D
,Marin T
,Dunlop S
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《Annals of Global Health》
Dynamic Field Theory of Executive Function: Identifying Early Neurocognitive Markers.
In this Monograph, we explored neurocognitive predictors of executive function (EF) development in a cohort of children followed longitudinally from 30 to 54 months of age. We tested predictions of a dynamic field model that explains development in a benchmark measure of EF development, the dimensional change card sort (DCCS) task. This is a rule-use task that measures children's ability to switch between sorting cards by shape or color rules. A key developmental mechanism in the model is that dimensional label learning drives EF development. Data collection began in February 2019 and was completed in April 2022 on the Knoxville campus of the University of Tennessee. Our cohort included 20 children (13 female) all of whom were White (not Hispanic/Latinx) from an urban area in southern United States, and the sample annual family income distribution ranged from low to high (most families falling between $40,000 and 59,000 per year (note that we address issues of generalizability and the small sample size throughout the monograph)). We tested the influence of dimensional label learning on DCCS performance by longitudinally assessing neurocognitive function across multiple domains at 30 and 54 months of age. We measured dimensional label learning with comprehension and production tasks for shape and color labels. Simple EF was measured with the Simon task which required children to respond to images of a cat or dog with a lateralized (left/right) button press. Response conflict was manipulated in this task based on the spatial location of the stimulus which could be neutral (central), congruent, or incongruent with the spatial lateralization of the response. Dimensional understanding was measured with an object matching task requiring children to generalize similarity between objects that matched within the dimensions of color or shape. We first identified neural measures associated with performance and development on each of these tasks. We then examined which of these measures predicted performance on the DCCS task at 54 months. We measured neural activity with functional near-infrared spectroscopy across bilateral frontal, temporal, and parietal cortices. Our results identified an array of neurocognitive mechanisms associated with development within each domain we assessed. Importantly, our results suggest that dimensional label learning impacts the development of EF. Neural activation in left frontal cortex during dimensional label production at 30 months of age predicted EF performance at 54 months of age. We discussed these results in the context of efforts to train EF with broad transfer. We also discussed a new autonomy-centered EF framework. The dynamic field model on which we have motivated the current research makes decisions autonomously and various factors can influence the types of decisions that the model makes. In this way, EF is a property of neurocognitive dynamics, which can be influenced by individual factors and contextual effects. We also discuss how this conceptual framework can generalize beyond the specific example of dimensional label learning and DCCS performance to other aspects of EF and how this framework can help to understand how EF unfolds in unique individual, cultural, and contextual factors. Measures of EF during early childhood are associated with a wide range of development outcomes, including academic skills and quality of life. The hope is that broad aspects of development can be improved by implementing interventions aimed at facilitating EF development. However, this promise has been largely unrealized. Previous work on EF development has been limited by a focus on EF components, such as inhibition, working memory, and switching. Similarly, intervention research has focused on practicing EF tasks that target these specific components of EF. While performance typically improves on the practiced task, improvement rarely generalizes to other EF tasks or other developmental outcomes. The current work is unique because we looked beyond EF itself to identify the lower-level learning processes that predict EF development. Indeed, the results of this study identify the first learning mechanism involved in the development of EF. Although the work here provides new targets for interventions in future work, there are also important limitations. First, our sample is not representative of the underlying population of children in the United States under the age of 5. This is a problem in much of the existing developmental cognitive neuroscience research. We discussed challenges to the generalizability of our findings to the population at large. This is particularly important given that our theory is largely contextual, suggesting that children's unique experiences with learning labels for visual dimensions will impact EF development. Second, we identified a learning mechanism to target in future intervention research; however, it is not clear whether such interventions would benefit all children or how to identify children who would benefit most from such interventions. We also discuss prospective lines of research that can address these limitations, such as targeting families that are typically underrepresented in research, expanding longitudinal studies to examine longer term outcomes such as school-readiness and academic skills, and using the dynamic field (DF) model to systematically explore how exposure to objects and labels can optimize the neural representations underlying dimensional label learning. Future work remains to understand how such learning processes come to define the contextually and culturally specific skills that emerge over development and how these skills lay the foundation for broad developmental trajectories.
McCraw A
,Sullivan J
,Lowery K
,Eddings R
,Heim HR
,Buss AT
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