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Chemicals Used in Plastic Materials: An Estimate of the Attributable Disease Burden and Costs in the United States

Trasande, Leonardo; Krithivasan, Roopa; Park, Kevin; Obsekov, Vladislav; Belliveau, Michael
Context: Chemicals used in plastics have been described to contribute to disease and disability, but attributable fractions have not been quantified to assess specific contributions. Without this information, interventions proposed as part of the Global Plastics Treaty cannot be evaluated for potential benefits. Objective: To accurately inform the tradeoffs involved in the ongoing reliance on plastic production as a source of economic productivity in the United States, we calculated the attributable disease burden and cost due to chemicals used in plastic materials in 2018. Methods: We first analyzed the existing literature to identify plastic-related fractions (PRF) of disease and disability for specific polybrominated diphenylethers (PBDE), phthalates, bisphenols, and polyfluoroalkyl substances and perfluoroalkyl substances (PFAS). We then updated previously published disease burden and cost estimates for these chemicals in the United States to 2018. By uniting these data, we computed estimates of attributable disease burden and costs due to plastics in the United States. Results: We identified PRFs of 97.5% for bisphenol A (96.25-98.75% for sensitivity analysis), 98% (96%-99%) for di-2-ethylhexylphthalate, 100% (71%-100%) for butyl phthalates and benzyl phthalates, 98% (97%-99%) for PBDE-47, and 93% (16%-96%) for PFAS. In total, we estimate $249 billion (sensitivity analysis: $226 billion-$289 billion) in plastic-attributable disease burden in 2018. The majority of these costs arose as a result of PBDE exposure, though $66.7 billion ($64.7 billion-67.3 billion) was due to phthalate exposure and $22.4 billion was due to PFAS exposure (sensitivity analysis: $3.85-$60.1 billion). Conclusion: Plastics contribute substantially to disease and associated social costs in the United States, accounting for 1.22% of the gross domestic product. The costs of plastic pollution will continue to accumulate as long as exposures continue at current levels. Actions through the Global Plastics Treaty and other policy initiatives will reduce these costs in proportion to the actual reductions in chemical exposures achieved.
SCOPUS:85182689935
ISSN: 2472-1972
CID: 5629102

Prenatal phthalate exposure and adverse birth outcomes in the USA: a prospective analysis of births and estimates of attributable burden and costs

Trasande, Leonardo; Nelson, Morgan E; Alshawabkeh, Akram; Barrett, Emily S; Buckley, Jessie P; Dabelea, Dana; Dunlop, Anne L; Herbstman, Julie B; Meeker, John D; Naidu, Mrudula; Newschaffer, Craig; Padula, Amy M; Romano, Megan E; Ruden, Douglas M; Sathyanarayana, Sheela; Schantz, Susan L; Starling, Anne P; Hamra, Ghassan B; ,
BACKGROUND:Phthalates are synthetic chemicals widely used in consumer products and have been identified to contribute to preterm birth. Existing studies have methodological limitations and potential effects of di-2-ethylhexyl phthalate (DEHP) replacements are poorly characterised. Attributable fractions and costs have not been quantified, limiting the ability to weigh trade-offs involved in ongoing use. We aimed to leverage a large, diverse US cohort to study associations of phthalate metabolites with birthweight and gestational age, and estimate attributable adverse birth outcomes and associated costs. METHODS:In this prospective analysis we used extant data in the US National Institutes of Health Environmental influences on Child Health Outcomes (ECHO) Program from 1998 to 2022 to study associations of 20 phthalate metabolites with gestational age at birth, birthweight, birth length, and birthweight for gestational age z-scores. We also estimated attributable adverse birth outcomes and associated costs. Mother-child dyads were included in the study if there were one or more urinary phthalate measurements during the index pregnancy; data on child's gestational age and birthweight; and singleton delivery. FINDINGS/RESULTS:increase were higher for phthalic acid (2·71 [1·91-3·83]), DiNP (2·25 [1·67-3·00]), DiDP (1·69 [1·25-2·28]), and DnOP (2·90 [1·96-4·23]). We estimated 56 595 (sensitivity analyses 24 003-120 116) phthalate-attributable preterm birth cases in 2018 with associated costs of US$3·84 billion (sensitivity analysis 1·63- 8·14 billion). INTERPRETATION/CONCLUSIONS:In a large, diverse sample of US births, exposure to DEHP, DiDP, DiNP, and DnOP were associated with decreased gestational age and increased risk of preterm birth, suggesting substantial opportunities for prevention. This finding suggests the adverse consequences of substitution of DEHP with chemically similar phthalates and need to regulate chemicals with similar properties as a class. FUNDING/BACKGROUND:National Institutes of Health.
PMID: 38331533
ISSN: 2542-5196
CID: 5632442

Endocrine-disrupting chemicals: Mainstream recognition of health effects and implications for the practicing internist

Trasande, Leonardo; Sargis, Robert M
Rapidly advancing evidence documents that a broad array of synthetic chemicals found ubiquitously in the environment contribute to disease and disability across the lifespan. Although the early literature focused on early life exposures, endocrine-disrupting chemicals (EDCs) are now understood to contribute substantially to chronic disease in adulthood, especially metabolic, cardiovascular, and reproductive consequences as well as endocrine cancers. The contribution to mortality is substantial, with over 90,000 deaths annually and at least $39 billion/year in lost economic productivity in the United States (US) due to exposure to certain phthalates that are used as plasticizers in food packaging. Importantly, exposures are disproportionately high in low-income and minoritized populations, driving disparities in these conditions. Though non-Hispanic Blacks and Mexican Americans comprise 12.6% and 13.5% of the US population, they bear 16.5% and 14.6% of the disease burden due to EDCs, respectively. Many of these exposures can be modified through safe and simple behavioral changes supported by proactive government action to both limit known hazardous exposures and to proactively screen new industrial chemicals prior to their use. Routine healthcare maintenance should include guidance to reduce EDC exposures, and a recent report by the Institute of Medicine suggests that testing be conducted, particularly in populations heavily exposed to perfluoroalkyl substances-chemicals used in nonstick coatings as well as oil- and water-resistant clothing.
PMID: 38037246
ISSN: 1365-2796
CID: 5617032

Frequency, morbidity and equity - the case for increased research on male fertility

Kimmins, Sarah; Anderson, Richard A; Barratt, Christopher L R; Behre, Hermann M; Catford, Sarah R; De Jonge, Christopher J; Delbes, Geraldine; Eisenberg, Michael L; Garrido, Nicolas; Houston, Brendan J; Jørgensen, Niels; Krausz, Csilla; Lismer, Ariane; McLachlan, Robert I; Minhas, Suks; Moss, Tim; Pacey, Allan; Priskorn, Lærke; Schlatt, Stefan; Trasler, Jacquetta; Trasande, Leonardo; Tüttelmann, Frank; Vazquez-Levin, Mónica Hebe; Veltman, Joris A; Zhang, Feng; O'Bryan, Moira K
Currently, most men with infertility cannot be given an aetiology, which reflects a lack of knowledge around gamete production and how it is affected by genetics and the environment. A failure to recognize the burden of male infertility and its potential as a biomarker for systemic illness exists. The absence of such knowledge results in patients generally being treated as a uniform group, for whom the strategy is to bypass the causality using medically assisted reproduction (MAR) techniques. In doing so, opportunities to prevent co-morbidity are missed and the burden of MAR is shifted to the woman. To advance understanding of men's reproductive health, longitudinal and multi-national centres for data and sample collection are essential. Such programmes must enable an integrated view of the consequences of genetics, epigenetics and environmental factors on fertility and offspring health. Definition and possible amelioration of the consequences of MAR for conceived children are needed. Inherent in this statement is the necessity to promote fertility restoration and/or use the least invasive MAR strategy available. To achieve this aim, protocols must be rigorously tested and the move towards personalized medicine encouraged. Equally, education of the public, governments and clinicians on the frequency and consequences of infertility is needed. Health options, including male contraceptives, must be expanded, and the opportunities encompassed in such investment understood. The pressing questions related to male reproductive health, spanning the spectrum of andrology are identified in the Expert Recommendation.
PMID: 37828407
ISSN: 1759-4820
CID: 5604772

Understanding risk and causal mechanisms for developing obesity in infants and young children: A National Institutes of Health workshop

Aagaard, Kjersti M; Barkin, Shari L; Burant, Charles F; Carnell, Susan; Demerath, Ellen; Donovan, Sharon M; Eneli, Ihuoma; Francis, Lori A; Gilbert-Diamond, Diane; Hivert, Marie-France; LeBourgeois, Monique K; Loos, Ruth J F; Lumeng, Julie C; Miller, Alison L; Okely, Anthony D; Osganian, Stavroula K; Ramirez, Amelie G; Trasande, Leonardo; Van Horn, Linda V; Wake, Melissa; Wright, Rosalind J; Yanovski, Susan Z
Obesity in children remains a major public health problem, with the current prevalence in youth ages 2-19 years estimated to be 19.7%. Despite progress in identifying risk factors, current models do not accurately predict development of obesity in early childhood. There is also substantial individual variability in response to a given intervention that is not well understood. On April 29-30, 2021, the National Institutes of Health convened a virtual workshop on "Understanding Risk and Causal Mechanisms for Developing Obesity in Infants and Young Children." The workshop brought together scientists from diverse disciplines to discuss (1) what is known regarding epidemiology and underlying biological and behavioral mechanisms for rapid weight gain and development of obesity and (2) what new approaches can improve risk prediction and gain novel insights into causes of obesity in early life. Participants identified gaps and opportunities for future research to advance understanding of risk and underlying mechanisms for development of obesity in early life. It was emphasized that future studies will require multi-disciplinary efforts across basic, behavioral, and clinical sciences. An exposome framework is needed to elucidate how behavioral, biological, and environmental risk factors interact. Use of novel statistical methods may provide greater insights into causal mechanisms.
PMID: 38204366
ISSN: 1467-789x
CID: 5631532

Understanding risk and causal mechanisms for developing obesity in infants and young children: A National Institutes of Health workshop

Aagaard, Kjersti M.; Barkin, Shari L.; Burant, Charles F.; Carnell, Susan; Demerath, Ellen; Donovan, Sharon M.; Eneli, Ihuoma; Francis, Lori A.; Gilbert-Diamond, Diane; Hivert, Marie France; LeBourgeois, Monique K.; Loos, Ruth J.F.; Lumeng, Julie C.; Miller, Alison L.; Okely, Anthony D.; Osganian, Stavroula K.; Ramirez, Amelie G.; Trasande, Leonardo; Van Horn, Linda V.; Wake, Melissa; Wright, Rosalind J.; Yanovski, Susan Z.
Obesity in children remains a major public health problem, with the current prevalence in youth ages 2"“19 years estimated to be 19.7%. Despite progress in identifying risk factors, current models do not accurately predict development of obesity in early childhood. There is also substantial individual variability in response to a given intervention that is not well understood. On April 29"“30, 2021, the National Institutes of Health convened a virtual workshop on "Understanding Risk and Causal Mechanisms for Developing Obesity in Infants and Young Children." The workshop brought together scientists from diverse disciplines to discuss (1) what is known regarding epidemiology and underlying biological and behavioral mechanisms for rapid weight gain and development of obesity and (2) what new approaches can improve risk prediction and gain novel insights into causes of obesity in early life. Participants identified gaps and opportunities for future research to advance understanding of risk and underlying mechanisms for development of obesity in early life. It was emphasized that future studies will require multi-disciplinary efforts across basic, behavioral, and clinical sciences. An exposome framework is needed to elucidate how behavioral, biological, and environmental risk factors interact. Use of novel statistical methods may provide greater insights into causal mechanisms.
SCOPUS:85181941209
ISSN: 1467-7881
CID: 5629942

Prenatal Exposure to Nonpersistent Environmental Chemicals and Postpartum Depression

Jacobson, Melanie H; Hamra, Ghassan B; Monk, Catherine; Crum, Rosa M; Upadhyaya, Sudhindra; Avalos, Lyndsay A; Bastain, Theresa M; Barrett, Emily S; Bush, Nicole R; Dunlop, Anne L; Ferrara, Assiamira; Firestein, Morgan R; Hipwell, Alison E; Kannan, Kurunthachalam; Lewis, Johnnye; Meeker, John D; Ruden, Douglas M; Starling, Anne P; Watkins, Deborah J; Zhao, Qi; Trasande, Leonardo; ,
IMPORTANCE/UNASSIGNED:Postpartum depression (PPD) affects up to 20% of childbearing individuals, and a significant limitation in reducing its morbidity is the difficulty in modifying established risk factors. Exposure to synthetic environmental chemicals found in plastics and personal care products, such as phenols, phthalates, and parabens, are potentially modifiable and plausibly linked to PPD and have yet to be explored. OBJECTIVE/UNASSIGNED:To evaluate associations of prenatal exposure to phenols, phthalates, parabens, and triclocarban with PPD symptoms. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This was a prospective cohort study from 5 US sites, conducted from 2006 to 2020, and included pooled data from 5 US birth cohorts from the National Institutes of Health Environmental Influences on Child Health Outcomes (ECHO) consortium. Participants were pregnant individuals with data on urinary chemical concentrations (phenols, phthalate metabolites, parabens, or triclocarban) from at least 1 time point in pregnancy and self-reported postnatal depression screening assessment collected between 2 weeks and 12 months after delivery. Data were analyzed from February to May 2022. EXPOSURES/UNASSIGNED:Phenols (bisphenols and triclosan), phthalate metabolites, parabens, and triclocarban measured in prenatal urine samples. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Depression symptom scores were assessed using the Edinburgh Postnatal Depression Scale (EPDS) or the Center for Epidemiologic Studies Depression Scale (CES-D), harmonized to the Patient-Reported Measurement Information System (PROMIS) Depression scale. Measures of dichotomous PPD were created using both sensitive (EPDS scores ≥10 and CES-D scores ≥16) and specific (EPDS scores ≥13 and CES-D scores ≥20) definitions. RESULTS/UNASSIGNED:Among the 2174 pregnant individuals eligible for analysis, nearly all (>99%) had detectable levels of several phthalate metabolites and parabens. PPD was assessed a mean (SD) of 3 (2.5) months after delivery, with 349 individuals (16.1%) and 170 individuals (7.8%) screening positive for PPD using the sensitive and specific definitions, respectively. Linear regression results of continuous PROMIS depression T scores showed no statistically significant associations with any chemical exposures. Models examining LMW and HMW phthalates and di (2-ethylhexyl) phthalate had estimates in the positive direction whereas all others were negative. A 1-unit increase in log-transformed LMW phthalates was associated with a 0.26-unit increase in the PROMIS depression T score (95% CI, -0.01 to 0.53; P = .06). This corresponded to an odds ratio (OR) of 1.08 (95% CI, 0.98-1.19) when modeling PPD as a dichotomous outcome and using the sensitive PPD definition. HMW phthalates were associated with increased odds of PPD (OR, 1.11; 95% CI, 1.00-1.23 and OR, 1.10; 95% CI, 0.96-1.27) for the sensitive and specific PPD definitions, respectively. Sensitivity analyses produced stronger results. CONCLUSIONS AND RELEVANCE/UNASSIGNED:Phthalates, ubiquitous chemicals in the environment, may be associated with PPD and could serve as important modifiable targets for preventive interventions. Future studies are needed to confirm these observations.
PMCID:10512164
PMID: 37728908
ISSN: 2168-6238
CID: 5620452

Bisphenol S, bisphenol F, bisphenol a exposure and body composition in US adults

Liu, Buyun; Yan, Yuxiang; Xie, Juan; Sun, Jian; Lehmler, Hans Joachim; Trasande, Leonardo; Wallace, Robert B.; Bao, Wei
Bisphenol S (BPS) and bisphenol F (BPF) are increasingly used to replace bisphenol A (BPA), an endocrine-disrupting chemical with putative obesogenic properties; whether and how BPS and BPF affect adiposity in humans remains to be determined. Therefore, we examined the association of BPA, BPS, and BPF with body composition among US adults. We included 1787 participants aged 20"“59 years old in the National Health and Nutrition Examination Survey 2013"“2016 who had information on urinary BPA, BPS, and BPF concentrations, and body composition measured using dual-energy x-ray absorptiometry. After full adjustment for potential confounders in linear regression models, BPA was significantly associated with the % body fat of the whole body, arm, and leg, with the β (95% CI) for the highest quartile vs. the lowest quartile of 1.34 (95%CI [0.11, 2.58], P = 0.03), 1.60 (95%CI [0.20, 3.00], P = 0.03), and 1.63 (95%CI [0.24, 3.02], P = 0.02), respectively. No association between BPA and lean mass was found. For BPS, significant associations were found for % body fat of the whole body (β [95% CI] = 1.42 [0.49, 2.36], P = 0.004), trunk (β[95% CI] = 1.92 [0.86, 2.97], P = 0.001), and arm (β [95% CI] = 1.60 [0.49, 2.70], P = 0.01), as well as lean mass of the whole body (β [95% CI] = 2610.6 [1324.3, 3896.8], P < 0.001), trunk (β [95% CI] = 1467.0 [745.3, 2188.7], P < 0.001), arm (β [95% CI] = 113.4 [10.3, 216.5], P = 0.03), and leg (β [95% CI] = 431.5 [219.6, 643.4], P < 0.001), comparing the third quartile vs. the lowest quartile. No significant association was observed between BPF and % body fat and lean mass. Results suggest that higher BPA levels were significantly associated with greater % body fat of the whole body and limbs, and there was suggestive evidence that BPS levels were associated with both % body fat and lean mass of the whole body and body parts in a nonmonotonic relationship.
SCOPUS:85176242980
ISSN: 0045-6535
CID: 5614602

Bisphenol S, bisphenol F, bisphenol a exposure and body composition in US adults

Liu, Buyun; Yan, Yuxiang; Xie, Juan; Sun, Jian; Lehmler, Hans-Joachim; Trasande, Leonardo; Wallace, Robert B; Bao, Wei
Bisphenol S (BPS) and bisphenol F (BPF) are increasingly used to replace bisphenol A (BPA), an endocrine-disrupting chemical with putative obesogenic properties; whether and how BPS and BPF affect adiposity in humans remains to be determined. Therefore, we examined the association of BPA, BPS, and BPF with body composition among US adults. We included 1787 participants aged 20-59 years old in the National Health and Nutrition Examination Survey 2013-2016 who had information on urinary BPA, BPS, and BPF concentrations, and body composition measured using dual-energy x-ray absorptiometry. After full adjustment for potential confounders in linear regression models, BPA was significantly associated with the % body fat of the whole body, arm, and leg, with the β (95% CI) for the highest quartile vs. the lowest quartile of 1.34 (95%CI [0.11, 2.58], P = 0.03), 1.60 (95%CI [0.20, 3.00], P = 0.03), and 1.63 (95%CI [0.24, 3.02], P = 0.02), respectively. No association between BPA and lean mass was found. For BPS, significant associations were found for % body fat of the whole body (β [95% CI] = 1.42 [0.49, 2.36], P = 0.004), trunk (β[95% CI] = 1.92 [0.86, 2.97], P = 0.001), and arm (β [95% CI] = 1.60 [0.49, 2.70], P = 0.01), as well as lean mass of the whole body (β [95% CI] = 2610.6 [1324.3, 3896.8], P < 0.001), trunk (β [95% CI] = 1467.0 [745.3, 2188.7], P < 0.001), arm (β [95% CI] = 113.4 [10.3, 216.5], P = 0.03), and leg (β [95% CI] = 431.5 [219.6, 643.4], P < 0.001), comparing the third quartile vs. the lowest quartile. No significant association was observed between BPF and % body fat and lean mass. Results suggest that higher BPA levels were significantly associated with greater % body fat of the whole body and limbs, and there was suggestive evidence that BPS levels were associated with both % body fat and lean mass of the whole body and body parts in a nonmonotonic relationship.
PMID: 38303380
ISSN: 1879-1298
CID: 5626862

Prenatal Phenol and Paraben Exposures and Adverse Birth Outcomes: A Prospective Analysis of U.S. Births

Trasande, Leonardo; Nelson, Morgan E; Alshawabkeh, Akram; Barrett, Emily S; Buckley, Jessie P; Dabelea, Dana; Dunlop, Anne L; Herbstman, Julie B; Meeker, John D; Naidu, Mrudula; Newschaffer, Craig; Padula, Amy M; Romano, Megan E; Ruden, Douglas M; Sathyanarayana, Sheela; Schantz, Susan L; Starling, Anne P; Etzel, Taylor; Hamra, Ghassan B; ,
BACKGROUND:Synthetic chemicals are increasingly being recognized for potential independent contributions to preterm birth (PTB) and low birth weight (LBW). Bisphenols, parabens, and triclosan are consumer product chemicals that act via similar mechanisms including estrogen, androgen, and thyroid disruption and oxidative stress. Multiple cohort studies have endeavored to examine effects on birth outcomes, and systematic reviews have been limited due to measurement of 1-2 spot samples during pregnancy and limited diversity of populations. OBJECTIVE:To study the effects of prenatal phenols and parabens on birth size and gestational age (GA) in 3,619 mother-infant pairs from 11 cohorts in the NIH Environmental influences on Child Health Outcomes program. RESULTS:pregnancy averaged concentration of 2,4-dichlorophenol was associated with 43% lower (95% CI: -67%, -2%) odds of low birthweight; the direction of effect was the same for the highly correlated 2,5-dichlorophenol, but with a smaller magnitude (-29%, 95% CI: -53%, 8%). DISCUSSION/CONCLUSIONS:In a large and diverse sample generally representative of the United States, benzophenone-3 and methylparaben were associated with lower birthweight as well as birthweight adjusted for gestational age and higher odds of SGA, while 2,4-dichlorophenol. These associations with smaller size at birth are concerning in light of the known consequences of intrauterine growth restriction for multiple important health outcomes emerging later in life.
PMID: 38181479
ISSN: 1873-6750
CID: 5624362