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Association Between Bisphenol A Exposure and Risk of All-Cause and Cause-Specific Mortality in US Adults

Bao, Wei; Liu, Buyun; Rong, Shuang; Dai, Susie Y; Trasande, Leonardo; Lehmler, Hans-Joachim
Importance/UNASSIGNED:Bisphenol A (BPA) is a major public health concern because of its high-volume industrial production, ubiquitous exposure to humans, and potential toxic effects on multiple organs and systems in humans. However, prospective studies regarding the association of BPA exposure with long-term health outcomes are sparse. Objective/UNASSIGNED:To examine the association of BPA exposure with all-cause mortality and cause-specific mortality among adults in the United States. Design, Setting, and Participants/UNASSIGNED:This nationally representative cohort study included 3883 adults aged 20 years or older who participated in the US National Health and Nutrition Examination Survey 2003-2008 and provided urine samples for BPA level measurements. Participants were linked to mortality data from survey date through December 31, 2015. Data analyses were conducted in July 2019. Exposures/UNASSIGNED:Urinary BPA levels were quantified using online solid-phase extraction coupled to high-performance liquid chromatography-isotope dilution tandem mass spectrometry. Main Outcomes and Measures/UNASSIGNED:Mortality from all causes, cardiovascular disease, and cancer. Results/UNASSIGNED:This cohort study included 3883 adults aged 20 years or older (weighted mean [SE] age, 43.6 [0.3] years; 2032 women [weighted, 51.4%]). During 36 514 person-years of follow-up (median, 9.6 years; maximum, 13.1 years), 344 deaths occurred, including 71 deaths from cardiovascular disease and 75 deaths from cancer. Participants with higher urinary BPA levels were at higher risk for death. After adjustment for age, sex, race/ethnicity, socioeconomic status, dietary and lifestyle factors, body mass index, and urinary creatinine levels, the hazard ratio comparing the highest vs lowest tertile of urinary BPA levels was 1.49 (95% CI, 1.01-2.19) for all-cause mortality, 1.46 (95% CI, 0.67-3.15) for cardiovascular disease mortality, and 0.98 (95% CI, 0.40-2.39) for cancer mortality. Conclusions and Relevance/UNASSIGNED:In this nationally representative cohort of US adults, higher BPA exposure was significantly associated with an increased risk of all-cause mortality. Further studies are needed to replicate these findings in other populations and determine the underlying mechanisms.
PMCID:7431989
PMID: 32804211
ISSN: 2574-3805
CID: 4572992

Endocrine-disrupting chemicals: implications for human health

Kahn, Linda G; Philippat, Claire; Nakayama, Shoji F; Slama, Rémy; Trasande, Leonardo
Since reports published in 2015 and 2016 identified 15 probable exposure-outcome associations, there has been an increase in studies in humans of exposure to endocrine-disrupting chemicals (EDCs) and a deepened understanding of their effects on human health. In this Series paper, we have reviewed subsequent additions to the literature and identified new exposure-outcome associations with substantial human evidence. Evidence is particularly strong for relations between perfluoroalkyl substances and child and adult obesity, impaired glucose tolerance, gestational diabetes, reduced birthweight, reduced semen quality, polycystic ovarian syndrome, endometriosis, and breast cancer. Evidence also exists for relations between bisphenols and adult diabetes, reduced semen quality, and polycystic ovarian syndrome; phthalates and prematurity, reduced anogenital distance in boys, childhood obesity, and impaired glucose tolerance; organophosphate pesticides and reduced semen quality; and occupational exposure to pesticides and prostate cancer. Greater evidence has accumulated than was previously identified for cognitive deficits and attention-deficit disorder in children following prenatal exposure to bisphenol A, organophosphate pesticides, and polybrominated flame retardants. Although systematic evaluation is needed of the probability and strength of these exposure-outcome relations, the growing evidence supports urgent action to reduce exposure to EDCs.
PMID: 32707118
ISSN: 2213-8595
CID: 4546172

Phthalate and Bisphenol Exposure during Pregnancy and Offspring Nonverbal IQ

van den Dries, Michiel A; Guxens, Mònica; Spaan, Suzanne; Ferguson, Kelly K; Philips, Elise; Santos, Susana; Jaddoe, Vincent W V; Ghassabian, Akhgar; Trasande, Leonardo; Tiemeier, Henning; Pronk, Anjoeka
BACKGROUND:Prenatal exposures to phthalates and bisphenols are associated with impaired brain development in animals. However, epidemiological studies investigating the association between prenatal phthalate or bisphenol exposure and cognition have produced mixed findings and mostly had modest sample sizes and measured the exposure during the third trimester. OBJECTIVE:We examined the association between pregnancy maternal urinary biomarkers of phthalate or bisphenol exposure and nonverbal intelligence quotient (IQ) in children 6 years of age. METHOD/METHODS: RESULTS: CONCLUSIONS:We did not observe that maternal biomarkers of bisphenol exposure are associated with nonverbal IQ. We found that phthalate exposure in early pregnancy and DNOP exposure in late pregnancy are associated with lower nonverbal IQ scores in children. Our results might suggest that particularly early pregnancy is a sensitive window of phthalate exposure, but future studies are needed to replicate our findings. https://doi.org/10.1289/EHP6047.
PMCID:7384796
PMID: 32716663
ISSN: 1552-9924
CID: 4540662

Endocrine-disrupting chemicals: economic, regulatory, and policy implications

Kassotis, Christopher D; Vandenberg, Laura N; Demeneix, Barbara A; Porta, Miquel; Slama, Remy; Trasande, Leonardo
Endocrine-disrupting chemicals (EDCs) substantially cost society as a result of increases in disease and disability but-unlike other toxicant classes such as carcinogens-have yet to be codified into regulations as a hazard category. This Series paper examines economic, regulatory, and policy approaches to limit human EDC exposures and describes potential improvements. In the EU, general principles for EDCs call for minimisation of human exposure, identification as substances of very high concern, and ban on use in pesticides. In the USA, screening and testing programmes are focused on oestrogenic EDCs exclusively, and regulation is strictly risk-based. Minimisation of human exposure is unlikely without a clear overarching definition for EDCs and relevant pre-marketing test requirements. We call for a multifaceted international programme (eg, modelled on the International Agency for Research in Cancer) to address the effects of EDCs on human health-an approach that would proactively identify hazards for subsequent regulation.
PMID: 32707119
ISSN: 2213-8595
CID: 4539822

Fetal exposure to bisphenols and phthalates and childhood bone mass: a population-based prospective cohort study

van Zwol-Janssens, Charissa; Trasande, Leonardo; Asimakopoulos, Alexandros G; Martinez-Moral, Maria-Pilar; Kannan, Kurunthachalam; Philips, Elise M; Rivadeneira, Fernando; Jaddoe, Vincent W V; Santos, Susana
BACKGROUND:Exposure to bisphenols and phthalates might influence bone health. We hypothesized that exposure to bisphenols and phthalates during fetal life has persistent effects on bone development. OBJECTIVES/OBJECTIVE:To analyze the associations of fetal exposure to bisphenols and phthalates with bone health in school-aged children. METHODS:Among 1,362 mother-child pairs participating in a population-based cohort study, we measured maternal urinary concentrations of bisphenols and phthalates at first, second and third trimester with high performance liquid chromatography electrospray ionization-tandem mass spectrometry. Total body bone mineral density (BMD) and bone area (BA) were measured using dual-energy X-ray absorptiometry (DXA) at 6 and 10 years, and were both used to calculate bone mineral content (BMC) and area-adjusted BMC (aBMC, a measure of volumetric BMD). RESULTS:and -0.12 (95% CI, -0.20 to -0.04) g). Maternal third trimester low molecular weight (LMW) phthalate concentrations were associated with higher aBMC at 6 years whereas, maternal third trimester di-n-octylphthalate (DNOP) concentrations were associated with lower aBMC at 10 years. However, these associations did not remain statistically significant after multiple testing correction. DISCUSSION/CONCLUSIONS:Maternal first trimester BPS concentrations are associated with lower BMD and aBMC in school-aged children. These findings should be considered as hypothesis generating and need further replication and exploration of potential underlying mechanisms.
PMID: 32668547
ISSN: 1096-0953
CID: 4525082

Persistent organic pollutant exposure and celiac disease: A pilot study

Gaylord, Abigail; Trasande, Leonardo; Kannan, Kurunthachalam; Thomas, Kristen M; Lee, Sunmi; Liu, Mengling; Levine, Jeremiah
Celiac disease affects approximately 1% of the population worldwide. Little is known about environmental factors that may modulate risk in genetically susceptible populations. Persistent organic pollutants (POPs) are known endocrine disruptors and, given the interplay between the endocrine and immune systems, are plausible contributors to celiac disease. The current study aims to elucidate the association between POPs and celiac disease. We conducted a single-site pilot study of 88 patients recruited from NYU Langone's Hassenfeld Children's Hospital outpatient clinic, 30 of which were subsequently diagnosed with celiac disease using standard serology and duodenal biopsy examination. Polybrominated diphenyl ether (PBDEs), perfluoroalkyl substances (PFASs), and p,p'-dichlorodiphenyldichloroethylene (DDE) and HLA-DQ genotype category were measured in blood serum and whole blood, respectively. Multivariable logistic regressions were used to obtain odds ratios for celiac disease associated with serum POP concentrations. Controlling for sex, race, age, BMI, and genetic susceptibility score, patients with higher serum DDE concentrations had 2-fold higher odds of celiac disease (95% CI: 1.08, 3.84). After stratifying by sex, we found higher odds of celiac disease in females with serum concentrations of DDE (OR = 13.0, 95% CI = 1.54, 110), PFOS (OR = 12.8, 95% CI = 1.17, 141), perfluorooctanoic acid (OR = 20.6, 95% CI = 1.13, 375) and in males with serum BDE153, a PBDE congener (OR = 2.28, 95% CI = 1.01, 5.18). This is the first study to report on celiac disease with POP exposure in children. These findings raise further questions of how environmental chemicals may affect autoimmunity in genetically susceptible individuals.
PMID: 32409013
ISSN: 1096-0953
CID: 4438232

Impacts of food contact chemicals on human health: a consensus statement [Editorial]

Muncke, Jane; Andersson, Anna-Maria; Backhaus, Thomas; Boucher, Justin M; Carney Almroth, Bethanie; Castillo Castillo, Arturo; Chevrier, Jonathan; Demeneix, Barbara A; Emmanuel, Jorge A; Fini, Jean-Baptiste; Gee, David; Geueke, Birgit; Groh, Ksenia; Heindel, Jerrold J; Houlihan, Jane; Kassotis, Christopher D; Kwiatkowski, Carol F; Lefferts, Lisa Y; Maffini, Maricel V; Martin, Olwenn V; Myers, John Peterson; Nadal, Angel; Nerin, Cristina; Pelch, Katherine E; Fernández, Seth Rojello; Sargis, Robert M; Soto, Ana M; Trasande, Leonardo; Vandenberg, Laura N; Wagner, Martin; Wu, Changqing; Zoeller, R Thomas; Scheringer, Martin
Food packaging is of high societal value because it conserves and protects food, makes food transportable and conveys information to consumers. It is also relevant for marketing, which is of economic significance. Other types of food contact articles, such as storage containers, processing equipment and filling lines, are also important for food production and food supply. Food contact articles are made up of one or multiple different food contact materials and consist of food contact chemicals. However, food contact chemicals transfer from all types of food contact materials and articles into food and, consequently, are taken up by humans. Here we highlight topics of concern based on scientific findings showing that food contact materials and articles are a relevant exposure pathway for known hazardous substances as well as for a plethora of toxicologically uncharacterized chemicals, both intentionally and non-intentionally added. We describe areas of certainty, like the fact that chemicals migrate from food contact articles into food, and uncertainty, for example unidentified chemicals migrating into food. Current safety assessment of food contact chemicals is ineffective at protecting human health. In addition, society is striving for waste reduction with a focus on food packaging. As a result, solutions are being developed toward reuse, recycling or alternative (non-plastic) materials. However, the critical aspect of chemical safety is often ignored. Developing solutions for improving the safety of food contact chemicals and for tackling the circular economy must include current scientific knowledge. This cannot be done in isolation but must include all relevant experts and stakeholders. Therefore, we provide an overview of areas of concern and related activities that will improve the safety of food contact articles and support a circular economy. Our aim is to initiate a broader discussion involving scientists with relevant expertise but not currently working on food contact materials, and decision makers and influencers addressing single-use food packaging due to environmental concerns. Ultimately, we aim to support science-based decision making in the interest of improving public health. Notably, reducing exposure to hazardous food contact chemicals contributes to the prevention of associated chronic diseases in the human population.
PMCID:7053054
PMID: 32122363
ISSN: 1476-069x
CID: 4386342

The association between prenatal exposure to perfluoroalkyl substances and childhood neurodevelopment

Spratlen, Miranda J; Perera, Frederica P; Lederman, Sally Ann; Rauh, Virginia A; Robinson, Morgan; Kannan, Kurunthachalam; Trasande, Leonardo; Herbstman, Julie
Perfluoroalkyl substances (PFAS) were among various persistent organic pollutants suspected to have been released during the collapse of the World Trade Center (WTC) on 9/11. Evidence on the association between prenatal PFAS exposure and child neurodevelopment is limited and inconsistent. This study evaluated the association between prenatal PFAS exposure and child cognitive outcomes measured at 5 different time points in a population prenatally exposed to the WTC disaster. The study population included 302 pregnant women in the Columbia University WTC birth cohort enrolled between December 13, 2001 and June 26, 2002 at three hospitals located near the WTC site: Beth Israel, St. Vincent's, and New York University Downtown. We evaluated the association between prenatal exposure to four PFAS (perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorohexanesulfonic acid (PFHxS), perfluorononanoic acid (PFNA)) and child neurodevelopment measured using the Bayley Scales of Infant Development (BSID-II) at approximately 1, 2 and 3 years of age and using The Wechsler Preschool and Primary Scale of Intelligence (WPPSI) at approximately 4 and 6 years of age. Geometric mean (range) concentrations of PFAS were 6.03 (1.05, 33.7), 2.31 (0.18, 8.14), 0.43 (<LOQ, 10.3) and 0.67 (<LOQ, 15.8) ng/mL for PFOS, PFOA, PFNA and PFHxS, respectively. Several PFAS were associated with increases in cognitive outcomes in females and overall (males and females combined). Child sex modified the association between PFOS and the mental development index measured using BSID-II, with the observed relationship being positive for females and negative for males. Through principal component analyses, we observed a negative relationship between PFNA and the psychomotor development index measured using BSID-II and the verbal IQ measured using WPPSI. Our results suggest a sex- and compound-specific relationship between prenatal PFAS exposures and childhood neurodevelopment.
PMID: 32272335
ISSN: 1873-6424
CID: 4379012

Associations of maternal phthalate and bisphenol urine concentrations during pregnancy with childhood blood pressure in a population-based prospective cohort study

Sol, Chalana M; Santos, Susana; Asimakopoulos, Alexandros G; Martinez-Moral, Maria-Pilar; Duijts, Liesbeth; Kannan, Kurunthachalam; Trasande, Leonardo; Jaddoe, Vincent W V
OBJECTIVES/OBJECTIVE:Fetal exposure to phthalates and bisphenols may lead to vascular developmental adaptations, which program later cardiovascular disease. We examined the associations of fetal exposure to phthalates and bisphenols with childhood blood pressure. METHODS:In a population-based, prospective cohort study among 1,064 mother-child pairs, we measured maternal urine phthalate and bisphenol concentrations in first, second and third trimester of pregnancy. We measured childhood blood pressure at the mean age of 9.7 years (standard deviation 0.2 years) old. Analyses were performed for the total group, and for boys and girls separately. RESULTS:Maternal urine phthalate concentrations were not associated with childhood blood pressure among boys. Higher third trimester maternal urine concentrations of high molecular weight phthalates (HMWP), di-2-ehtylhexylphthalate (DEHP) and di-n-octylphthalate (DNOP) were associated with lower systolic and diastolic blood pressure among girls (p-values < 0.01). Also, higher second trimester maternal urine total bisphenol and bisphenol A concentrations were associated with higher systolic blood pressure among boys (p values < 0.01), but tended to be associated with a lower diastolic blood pressure among girls. CONCLUSIONS:Our results suggest sex-dependent associations of maternal urine phthalate and bisphenol concentrations during pregnancy with childhood blood pressure. Further studies are needed to explore the underlying mechanisms and long term consequences.
PMID: 32220816
ISSN: 1873-6750
CID: 4371162

The NYU Children's Health and Environment Study

Trasande, Leonardo; Ghassabian, Akhgar; Kahn, Linda G; Jacobson, Melanie H; Afanasyeva, Yelena; Liu, Mengling; Chen, Yu; Naidu, Mrudula; Alcedo, Garry; Gilbert, Joseph; Koshy, Tony T
The aims of the NYU Children's Health and Environment Study (CHES) are to evaluate influences of prenatal non-persistent chemical exposures on fetal and postnatal growth and pool our data with the US National Institutes of Health Environmental influences on Child Health Outcomes (ECHO) Program to answer collaborative research questions on the impact of the preconceptual, prenatal, and postnatal environment on childhood obesity, neurodevelopment, pre/peri/postnatal outcomes, upper and lower airway outcomes, and positive health. Eligible women were ≥ 18 years old, < 18 weeks pregnant, had a pregnancy that is not medically threatened, and planned to deliver at NYU Langone Hospital-Manhattan, Bellevue Hospital, or NYU Langone Hospital-Brooklyn. Between March 22, 2016 and April 15, 2019, we recruited 2469 pregnant women, from whom 2193 completed an initial questionnaire and continued into NYU CHES. Of the 2193, 88 miscarried, 28 terminated, and 20 experienced stillbirth, while 57 were lost to follow up. We report here demographic and other characteristics of the 2000 live deliveries (2037 children), from whom 1624 (80%) consented to postnatal follow-up. Data collection in pregnancy was nested in clinical care, with questionnaire and specimen collection conducted during routine prenatal visits at < 18, 18-25, and > 25 weeks gestation. These have been followed by questionnaire and specimen collection at birth and regular postpartum intervals.
PMID: 32212050
ISSN: 1573-7284
CID: 4357962