Dataset Information

Association of Exposure to Persistent Organic Pollutants With Mortality Risk: An Analysis of Data From the Prospective Investigation of Vasculature in Uppsala Seniors (PIVUS) Study.

ABSTRACT:

Importance

It has been suggested that persistent organic pollutants (POPs) are harmful to human health.

Objective

To investigate if POP levels in plasma are associated with future mortality.

Design, setting, and participants

Cohort study using data from the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study, collected between May 2001 and June 2004 when participants reached age 70 years. Participants were followed up for 5 years after the first examination. Mortality was tracked from age 70 to 80 years. Data analysis was conducted in January and February 2018.

Exposures

Eighteen POPs identified by the Stockholm Convention, including polychlorinated biphenyls (PCBs), organochlorine pesticides, and a brominated flame retardant, were measured in plasma levels by gas chromatography-mass spectrometry.

Main outcomes and measures

All-cause mortality.

Results

The study sample initially included 992 individuals (497 [50.1%] men) aged 70 years, who were examined between 2001 and 2004. At the second examination 5 years later, 814 individuals (82.1%; 412 [50.7%] women) completed follow-up. During a follow-up period of 10.0 years, 158 deaths occurred. When updated information on POP levels at ages 70 and 75 years was associated with all-cause mortality using Cox proportional hazard analyses, a significant association was found between hexa-chloro- through octa-chloro-substituted (highly chlorinated) PCBs and all-cause mortality (except PCB 194). The most significant association was observed for PCB 206 (hazard ratio [HR] for 1-SD higher natural log-transformed circulating PCB 206 levels, 1.55; 95% CI, 1.26-1.91; P?Conclusions and relevanceHigher levels of highly chlorinated PCBs were associated with an increased mortality risk, especially from cardiovascular diseases. These results suggest that public health actions should be undertaken to minimize exposure to highly chlorinated PCBs.

SUBMITTER: Lind PM

PROVIDER: S-EPMC6487572 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Association of Exposure to Persistent Organic Pollutants With Mortality Risk: An Analysis of Data From the Prospective Investigation of Vasculature in Uppsala Seniors (PIVUS) Study.

Lind P Monica PM Salihovic Samira S Stubleski Jordan J Kärrman Anna A Lind Lars L

JAMA network open 20190405 4

<h4>Importance</h4>It has been suggested that persistent organic pollutants (POPs) are harmful to human health.<h4>Objective</h4>To investigate if POP levels in plasma are associated with future mortality.<h4>Design, setting, and participants</h4>Cohort study using data from the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study, collected between May 2001 and June 2004 when participants reached age 70 years. Participants were followed up for 5 years a ...[more]

PMID: 31026035

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Project description:BackgroundPrenatal exposure to persistent organic pollutants (POPs) may contribute to the development of childhood obesity and metabolic disorders. However, little is known about whether the maternal nutritional status during pregnancy can modulate these associations.ObjectivesThe main objective was to characterize the joint associations and interactions between prenatal levels of POPs and nutrients on childhood obesity.MethodsWe used data from to the Spanish INfancia y Medio Ambiente-Environment and Childhood (INMA) birth cohort, on POPs and nutritional biomarkers measured in maternal blood collected at the first trimester of pregnancy and child anthropometric measurements at 7 years of age. Six organochlorine compounds (OCs) [dichlorodiphenyldichloroethylene, hexachlorobenzene (HCB), β-hexachlorocyclohexane (β-HCH) and polychlorinated biphenyls 138, 153, 180] and four per- and polyfluoroalkyl substances (PFAS) were measured. Nutrients included vitamins (D, B12, and folate), polyunsaturated fatty acids (PUFAs), and dietary carotenoids. Two POPs-nutrients mixtures data sets were established: a) OCs, PFAS, vitamins, and carotenoids (n=660), and b) OCs, PUFAs, and vitamins (n=558). Joint associations of mixtures on obesity were characterized using Bayesian kernel machine regression (BKMR). Relative importance of biomarkers and two-way interactions were identified using gradient boosting machine, hierarchical group lasso regularization, and BKMR. Interactions were further characterized using multivariate regression models in the multiplicative and additive scale.ResultsForty percent of children had overweight or obesity. We observed a positive overall joint association of both POPs-nutrients mixtures on overweight/obesity risk, with HCB and vitamin B12 the biomarkers contributing the most. Recurrent interactions were found between HCB and vitamin B12 across screening models. Relative risk for a natural log increase of HCB was 1.31 (95% CI: 1.11, 1.54, pInteraction=0.02) in the tertile 2 of vitamin B12 and in the additive scale a relative excess risk due to interaction of 0.11 (95% CI: 0.02, 0.20) was found. Interaction between perfluorooctane sulfonate and β-cryptoxanthin suggested a protective effect of the antioxidant on overweight/obesity risk.ConclusionThese results support that maternal nutritional status may modulate the effect of prenatal exposure to POPs on childhood overweight/obesity. These findings may help to develop a biological hypothesis for future toxicological studies and to better interpret inconsistent findings in epidemiological studies. https://doi.org/10.1289/EHP11258.

Project description:The incidence of neurodevelopmental and neurodegenerative diseases worldwide has dramatically increased over the last decades. Although the aetiology remains uncertain, evidence is now growing that exposure to persistent organic pollutants during sensitive neurodevelopmental periods such as early life may be a strong risk factor, predisposing the individual to disease development later in life. Epidemiological studies have associated environmentally persistent organic pollutant exposure to brain disorders including neuropathies, cognitive, motor, and sensory impairments; neurodevelopmental disorders such as autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD); and neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS). In many ways, this expands the classical "Developmental Origins of Health and Disease" paradigm to include exposure to pollutants. This model has been refined over the years to give the current "three-hit" model that considers the individual's genetic factors as a first "hit." It has an immediate interaction with the early-life exposome (including persistent organic pollutants) that can be considered to be a second "hit." Together, these first two "hits" produce a quiescent or latent phenotype, most probably encoded in the epigenome, which has become susceptible to a third environmental "hit" in later life. It is only after the third "hit" that the increased risk of disease symptoms is crystallised. However, if the individual is exposed to a different environment in later life, they would be expected to remain healthy. In this review, we examine the effect of exposure to persistent organic pollutants and particulate matters in early life and the relationship to subsequent neurodevelopmental and neurodegenerative disorders. The roles of those environmental factors which may affect epigenetic DNA methylation and therefore influence normal neurodevelopment are then evaluated.

Dataset Information

Association of Exposure to Persistent Organic Pollutants With Mortality Risk: An Analysis of Data From the Prospective Investigation of Vasculature in Uppsala Seniors (PIVUS) Study.

Importance

Objective

Design, setting, and participants

Exposures

Main outcomes and measures

Results

Publications

Association of Exposure to Persistent Organic Pollutants With Mortality Risk: An Analysis of Data From the Prospective Investigation of Vasculature in Uppsala Seniors (PIVUS) Study.

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