Sociodemographic and dietary determinants of glyphosate exposure in a NYC-based pregnancy cohort.

Previous studies have provided evidence for associations between glyphosate and aminomethylphosphonic acid (AMPA) exposure and adverse birth outcomes. However, few pregnancy cohort studies have investigated dietary and other determinants of glyphosate and AMPA exposure. We aimed to identify dietary and sociodemographic factors that predict glyphosate and AMPA exposure in a contemporary, urban pregnancy cohort in the US. The study included 725 pregnant participants from the New York University Children's Health and Environment Study (NYU CHES) in New York City. Urinary concentrations of glyphosate and AMPA, determined by high-performance liquid chromatography and tandem mass spectrometry, were analyzed in urine collected from NYU CHES participants across three prenatal time points. The Diet Health Questionnaire II was completed to capture dietary intake during the prenatal period. Descriptive statistics and bivariate linear models were used to assess determinants of urinary glyphosate and AMPA concentrations. Median urinary glyphosate and AMPA levels were 0.36 ng/mL and 0.37 ng/mL, respectively. Lower glyphosate levels were associated with younger age, obesity, public insurance, being single, and lower educational attainment. Nuts, seeds and whole grain intake was associated with increased urinary glyphosate concentrations. Urinary glyphosate concentrations were lower in summer than in winter. The study findings highlight widespread exposure to glyphosate and AMPA in this pregnancy cohort, with nuts/seeds and whole grains identified as possible dietary sources of exposure. High detection rates in the study population necessitate further research on dietary exposure patterns and perinatal outcomes to inform targeted interventions and reduce exposure in vulnerable populations.

Redlining in New York City: impacts on particulate matter exposure during pregnancy and birth outcomes.

BACKGROUND: Evidence suggests historical redlining shaped the built environment and health outcomes in urban areas. Only a handful of studies have examined redlining's association with air pollution and adverse birth outcomes in New York City (NYC). Additionally, no NYC-specific studies have examined the impact of redlining on birth weight. METHODS: This longitudinal cohort study analysed data from the National Institute of Health Environmental Influences on Child Health Outcomes Programme to investigate the extent to which maternal residence in a historically redlined neighbourhood is associated with fine particulate matter (PM2.5) exposure during pregnancy using multivariable regression models. Additionally, we examined how maternal residence in a historically redlined neighbourhood during pregnancy influenced birth weight z-score, preterm birth and low birth weight. RESULTS: Our air pollution model showed that living in a historically redlined census tract or an ungraded census tract was associated with increased PM2.5 exposure during pregnancy. We also found living in a historically redlined census tract or an ungraded census tract was associated with a lower birth weight z-score. This finding remained significant when controlling for individual and census tract-level race, ethnicity and income. When we controlled PM2.5 in our models assessing the relationship between redlining grade and birth outcome, our results did not change. DISCUSSION: Our study supports the literature linking redlining to contemporary outcomes. However, our research in ungraded tracts suggests redlining alone is insufficient to fully explain inequality in birth outcomes and PM2.5 levels today.

Associations of bisphenol and phthalate exposure and anti-Müllerian hormone levels in women of reproductive age.

Background: In women, exposure to endocrine disrupting chemicals might accelerate the depletion of the ovarian reserve and might be associated with accelerative reproductive aging and fertility. We examined the longitudinal associations of exposure to bisphenols and phthalates with anti-Müllerian hormone concentrations. Methods: Pregnant women of 18 years or older that resided in Rotterdam between 2002 and 2006 were eligible for participation in this longitudinal prospective cohort study. We measured urinary bisphenol and phthalate concentration at three time-points in pregnancy among 1405 women, of whom 1322 women had serum Anti-Müllerian Hormone (AMH) measurements 6 and/or 9 years postpartum. We performed linear regression models to assess the association of urinary bisphenol and phthalate metabolites with AMH after 6 and 9 years, and linear mixed-effect model to assess the association with AMH over time. Models were adjusted for sociodemographic and lifestyle factors. Findings: In our multivariable linear regression models we observed associations of higher urinary pregnancy-averaged mono-isobutyl phthalate (mIBP), mono-(2-ethyl-5-oxohexyl) phthalate (mEOHP), and monobenzyl phthalate (mBzBP) with lower serum AMH after both 6 and 9 years. However, these associations did not remain after adjustment for multiple testing. No significant associations of bisphenol A with AMH were present in our study sample. In our linear mixed-effects models, higher mIBP, mono-(2-ethyl-5-hydroxyhexyl) phthalate (mEHHP), mEOHP, and mBzBP were associated with lower overall AMH levels (differences -0.07 (95% CI -0.13, -0.02), -0.09 (-0.15, -0.02), -0.08 (95% CI -0.14, -0.02), and -0.08 (-0.13, -0.03) µg/L per doubling in mIBP, mEHHP, mEOHP, and mBzBP respectively) (all False Discovery Rate adjusted p-values < 0.05). Interpretation: We identify decreases in indices of ovarian reserve in relationship to prenatal phthalate exposures. Studies are needed replicating our results among large multi-ethnic non-pregnant populations and assessing transgenerational effects of exposure on ovarian reserve. Funding: This study was supported by the Erasmus Medical Center and Erasmus University Rotterdam, the Netherlands Organisation for Health Research and Development, the European Research Council, the Dutch Heart Foundation, the Dutch Diabetes Foundation, the European Union's Horizon 2020 Research and Innovation Program, the National Institutes of Health, Ansh Labs Webster, and the Royal Netherlands Academy of Arts and Sciences.

Prenatal organophosphate pesticide exposure and sex-specific estimated Fetal size.

Prenatal organophosphate (OP) pesticide exposure may be associated with reduced fetal growth, although studies are limited and have mixed results. We investigated associations between prenatal OP pesticide exposure and fetal size and modification by fetal sex. Maternal urinary concentrations of dialkyl phosphate (DAP) metabolites were measured at three time points. Fetal biometrics were obtained from ultrasounds in the second (n=773) and third (n=535) trimesters. Associations between pregnancy-averaged ΣDAP and fetal biometry z-scores were determined through multiple linear regression. Modification by sex was investigated through stratification and interaction. In the second trimester, one ln-unit increase in ΣDAP was associated with lower estimated fetal weight (-0.15 SD; 95% CI: -0.29, -0.01), head circumference (-0.11 SD; CI: -0.22, 0.01), biparietal diameter (-0.14 SD; CI: -0.27, -0.01), and abdominal circumference (-0.12 SD; CI: -0.26, 0.01) in females. In the third trimester, one ln-unit increase in ΣDAP was associated with lower head circumference (-0.14 SD; CI: -0.28, 0.00) and biparietal diameter (-0.12 SD; CI: -0.26, 0.03) in males. Our results suggest that prenatal OP pesticide exposure is negatively associated with fetal growth in a sex-specific manner, with associations present for females in mid-gestation and males in late gestation.

Prenatal exposure to non-persistent chemicals and fetal-to-childhood growth trajectories.

INTRODUCTION: Prenatal exposure to non-persistent chemicals, including organophosphate pesticides, phthalates, and bisphenols, is associated with altered fetal and childhood growth. Few studies have examined these associations using longitudinal growth trajectories or considering exposure to chemical mixtures. METHODS: Among 777 participants from the Generation R Study, we used growth mixture models to identify weight and body mass index (BMI) trajectories using weight and height measures collected from the prenatal period to age 13. We measured exposure biomarkers for organophosphate pesticides, phthalates, and bisphenols in maternal urine at three timepoints during pregnancy. Multinomial logistic regression was used to estimate associations between averaged exposure biomarker concentrations and growth trajectories. We used quantile g-computation to estimate joint associations with growth trajectories. RESULTS: Phthalic acid (OR: 1.4, 95% CI: 1.01, 1.9) and bisphenol A (BPA; OR: 1.5, 95% CI: 1.0, 2.2) were associated with higher odds of a growth trajectory characterized by smaller prenatal and larger childhood weight relative to a referent trajectory of larger prenatal and average childhood weight. Biomarkers of organophosphate pesticides, individually and jointly, were associated with lower odds of a growth trajectory characterized by average prenatal and lower childhood weight. CONCLUSIONS: Exposure to phthalates and BPA was positively associated with a weight trajectory characterized by lower prenatal and higher childhood weight, while exposure to organophosphate pesticides was negatively associated with a trajectory of average prenatal and lower childhood weight. This study is consistent with the hypothesis that non-persistent chemical exposures disrupt growth trajectories from the prenatal period through childhood.

Exposure to Endocrine Disruptors in Early life and Neuroimaging Findings in Childhood and Adolescence: a Scoping Review.

PURPOSE OF REVIEW: Evidence suggests neurotoxicity of endocrine disrupting chemicals (EDCs) during sensitive periods of development. We present an overview of pediatric population neuroimaging studies that examined brain influences of EDC exposure during prenatal period and childhood. RECENT FINDINGS: We found 46 studies that used magnetic resonance imaging (MRI) to examine brain influences of EDCs. These studies showed associations of prenatal exposure to phthalates, organophosphate pesticides (OPs), polyaromatic hydrocarbons and persistent organic pollutants with global and regional brain structural alterations. Few studies suggested alteration in functional MRI associated with prenatal OP exposure. However, studies on other groups of EDCs, such as bisphenols, and those that examined childhood exposure were less conclusive. These findings underscore the potential profound and lasting effects of prenatal EDC exposure on brain development, emphasizing the need for better regulation and strategies to reduce exposure and mitigate impacts. More studies are needed to examine the influence of postnatal exposure to EDC on brain imaging.

Urinary polycyclic aromatic hydrocarbon (PAH) metabolite concentrations in three pregnancy cohorts from 7 U.S. study sites.

OBJECTIVE: Prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with adverse birth and developmental outcomes in children. We aimed to describe prenatal PAH exposures in a large, multisite U.S. consortium. METHODS: We measured 12 mono-hydroxylated metabolites (OH-PAHs) of 7 PAHs (naphthalene, fluorene, phenanthrene, pyrene, benzo(c)phenanthrene, chrysene, benz(a)anthracene) in mid-pregnancy urine of 1,892 pregnant individuals from the ECHO PATHWAYS consortium cohorts: CANDLE (n = 988; Memphis), TIDES (n = 664; Minneapolis, Rochester, San Francisco, Seattle) and GAPPS (n = 240; Seattle and Yakima, WA). We described concentrations of 8 OH-PAHs of non-smoking participants (n = 1,695) by site, socioeconomic characteristics, and pregnancy stage (we report intraclass correlation coefficients (ICC) for n = 677 TIDES participants). RESULTS: Exposure to the selected PAHs was ubiquitous at all sites. 2-hydroxynaphthalene had the highest average concentrations at all sites. CANDLE had the highest average concentrations of most metabolites. Among non-smoking participants, we observed some patterns by income, education, and race but these were not consistent and varied by site and metabolite. ICCs of repeated OH-PAH measures from TIDES participants were ≤ 0.51. CONCLUSION: In this geographically-diverse descriptive analysis of U.S. pregnancies, we observed ubiquitous exposure to low molecular weight PAHs, highlighting the importance of better understanding PAH sources and their pediatric health outcomes attributed to early life PAH exposure.

The role of plastics in allergy, immunology, and human health: What the clinician needs to know and can do about it.

The effects of plastics on human health include allergy, atopy, asthma, and immune disruption, but the consequences of chemicals used in plastic materials span nearly every organ system and age group as well. Behavioral interventions to reduce plastic chemical exposures have reduced exposure in low- and high-income populations, yet health care providers know little about plastic chemical effects and seldom offer steps to patients to limit exposure. Health care facilities also use many products that increase the risk of chemical exposures, particularly for at-risk populations such as children in neonatal intensive care units. Given that disparities in plastic chemical exposure are well documented, collaborative efforts are needed between scientists and health care organizations, to develop products that improve provider knowledge about chemicals used in plastic materials and support the use of safer alternatives in medical devices and other equipment.

Elevated thyroid manganese reduces thyroid iodine to induce hypothyroidism in mice, but not rats, lacking SLC30A10 transporter.

Elevated manganese (Mn) accumulates in the brain and induces neurotoxicity. SLC30A10 is an Mn efflux transporter that controls body Mn levels. We previously reported that full-body Slc30a10 knockout mice (1) recapitulate the body Mn retention phenotype of humans with loss-of-function SLC30A10 mutations and (2) unexpectedly develop hypothyroidism induced by Mn accumulation in the thyroid, which reduces intra-thyroid thyroxine. Subsequent analyses of National Health and Nutrition Examination Survey data identified an association between serum Mn and subclinical thyroid changes. The emergence of thyroid deficits as a feature of Mn toxicity suggests that changes in thyroid function may be an underappreciated, but critical, modulator of Mn-induced disease. To better understand the relationship between thyroid function and Mn toxicity, here we further defined the mechanism of Mn-induced hypothyroidism using mouse and rat models. Slc30a10 knockout mice exhibited a profound deficit in thyroid iodine levels that occurred contemporaneously with increases in thyroid Mn levels and preceded the onset of overt hypothyroidism. Wild-type Mn-exposed mice also exhibited increased thyroid Mn levels, an inverse correlation between thyroid Mn and iodine levels, and subclinical hypothyroidism. In contrast, thyroid iodine levels were unaltered in newly generated Slc30a10 knockout rats despite an increase in thyroid Mn levels, and the knockout rats were euthyroid. Thus, Mn-induced thyroid dysfunction in genetic or Mn exposure-induced mouse models occurs due to a reduction in thyroid iodine subsequent to an increase in thyroid Mn levels. Moreover, rat and mouse thyroids have differential sensitivities to Mn, which may impact the manifestations of Mn-induced disease in these routinely used animal models.

Evaluating associations of bisphenol and phthalate exposure with time to pregnancy and subfecundity in a New York City pregnancy cohort.

It is important to understand the impact of consumer chemical exposure and fecundity, a couple's measure of probability of successful conception, given approximately 15% of couples experience infertility. Prior research has generally found null associations between bisphenol and phthalate exposure and fecundability, measured via time to pregnancy (TTP). However, this research has not been updated with current chemical exposures and have often lacked diversity in their study populations. We evaluated the associations between common bisphenol and phthalate chemical exposure groups and TTP as well as subfecundity (TTP>12 months) in the New York University Children's Health Study, a diverse pregnancy cohort from 2016 onward. Using first-trimester spot-urine samples to measure chemical exposure and self-reported TTP from first-trimester questionnaires, we observed a significant adverse association between total bisphenol exposure and certain phthalate groups on TTP and odds of subfecundity. Furthermore, in a mixtures analysis to explore the joint effects of the chemical groups on the outcomes, we found evidence of a potential interaction between total bisphenol exposure and low-molecular weight phthalates on TTP. Future research should continue to update our knowledge regarding the complex and potentially interacting effects of these chemicals on reproductive health.

Reproducibility between preschool and school-age Social Responsiveness Scale forms in the Environmental influences on Child Health Outcomes program.

Evidence suggests core autism trait consistency in older children, but development of these traits is variable in early childhood. The Social Responsiveness Scale (SRS) measures autism-related traits and broader autism phenotype, with two age-dependent forms in childhood (preschool, 2.5-4.5 years; school age, 4-18 years). Score consistency has been observed within forms, though reliability across forms has not been evaluated. Using data from the Environmental Influences on Child Health Outcomes (ECHO) program (n = 853), preschool, and school-age SRS scores were collected via maternal report when children were an average of 3.0 and 5.8 years, respectively. We compared reproducibility of SRS total scores (T-scores) and agreement above a clinically meaningful cutoff (T-scores ≥ 60) and examined predictors of discordance in cutoff scores across forms. Participant scores across forms were similar (mean difference: 3.3 points; standard deviation: 7), though preschool scores were on average lower than school-age scores. Most children (88%) were classified below the cutoff on both forms, and overall concordance was high (92%). However, discordance was higher in cohorts following younger siblings of autistic children (16%). Proportions of children with an autism diagnoses were also higher among those with discordant scores (27%) than among those with concordant scores (4%). Our findings indicate SRS scores are broadly reproducible across preschool and school-age forms, particularly for capturing broader, nonclinical traits, but also suggest that greater variability of autism-related traits in preschool-age children may reduce reliability with later school-age scores for those in the clinical range.

Longitudinal study of birthweight, blood pressure, and markers of arterial stiffness in children age six among the TIDES cohort.

OBJECTIVE: Although some studies have observed an association between birthweight and cardiovascular disease in adulthood, fewer have investigated whether birthweight is linked to cardiovascular health in early childhood. This study assesses the association between birthweight and cardiovascular outcomes in children 6 years of age. STUDY DESIGN: Birthweight, blood pressure (BP), and markers of arterial stiffness in children, including brachial artery distensibility and carotid-femoral pulse wave velocity (cfPWV), were obtained from 324 participants in The Infant Development and the Environment Study, a prospective multisite pregnancy cohort. Birthweight was converted into sex-specific birthweight-for-gestational-age (bw/ga) z -scores based on the INTERGROWTH-21st standard. Following 2017 American Academy of Pediatrics guidelines, SBP and DBP were transformed into sex, age, and height-specific z -scores. Associations between birthweight and cardiovascular outcomes were assessed using nested multivariable linear regression models among the overall and sex-stratified samples. RESULTS: Among the overall sample, bw/ga z -score was positively associated with cfPWV [b = 0.11 m/s, 95% confidence interval (CI): 0.01 m/s, 0.21 m/s] in crude and adjusted models. No associations between birthweight and cardiovascular outcomes were detected among the sex-stratified analyses. CONCLUSION: Overall, birthweight was not related to cardiovascular outcomes in children 6 years old. However, infants born with a higher birthweight may be at risk for higher cfPWV in childhood. Early intervention in pregnant people at risk of delivering high birthweight infants may be warranted if results are replicated.

Urinary concentrations of phthalate metabolites in relation to preeclampsia and other hypertensive disorders of pregnancy in the environmental influences on child health outcomes (ECHO) program.

BACKGROUND: Phthalate exposure may contribute to hypertensive disorders of pregnancy (HDP), including preeclampsia/eclampsia (PE/E), but epidemiologic studies are lacking. OBJECTIVES: To evaluate associations of pregnancy phthalate exposure with development of PE/E and HDP. METHODS: Using data from 3,430 participants in eight Environmental influences on Child Health Outcomes (ECHO) Program cohorts (enrolled from 1999 to 2019), we quantified concentrations of 13 phthalate metabolites (8 measured in all cohorts, 13 in a subset of four cohorts) in urine samples collected at least once during pregnancy. We operationalized outcomes as PE/E and composite HDP (PE/E and/or gestational hypertension). After correcting phthalate metabolite concentrations for urinary dilution, we evaluated covariate-adjusted associations of individual phthalates with odds of PE/E or composite HDP via generalized estimating equations, and the phthalate mixture via quantile-based g-computation. We also explored effect measure modification by fetal sex using stratified models. Effect estimates are reported as odds ratios (OR) with 95% confidence intervals (95% CIs). RESULTS: In adjusted analyses, a doubling of mono-benzyl phthalate (MBzP) and of mono (3-carboxypropyl) phthalate (MCPP) concentrations was associated with higher odds of PE/E as well as composite HDP, with somewhat larger associations for PE/E. For example, a doubling of MCPP was associated with 1.12 times the odds of PE/E (95%CI 1.00, 1.24) and 1.02 times the odds of composite HDP (95%CI 1.00, 1.05). A quartile increase in the phthalate mixture was associated with 1.27 times the odds of PE/E (95%CI 0.94, 1.70). A doubling of mono-carboxy isononyl phthalate (MCiNP) and of mono-carboxy isooctyl phthalate (MCiOP) concentrations were associated with 1.08 (95%CI 1.00, 1.17) and 1.11 (95%CI 1.03, 1.19) times the odds of PE/E. Effect estimates for PE/E were generally larger among pregnancies carrying female fetuses. DISCUSSION: In this study, multiple phthalates were associated with higher odds of PE/E and HDP. Estimates were precise and some were low in magnitude. Interventions to reduce phthalate exposures during pregnancy may help mitigate risk of these conditions.

Fetal bisphenol and phthalate exposure and early childhood growth in a New York City birth cohort.

BACKGROUND: Exposure to endocrine-disrupting chemicals such as bisphenols and phthalates during pregnancy may disrupt fetal developmental programming and influence early-life growth. We hypothesized that prenatal bisphenol and phthalate exposure was associated with alterations in adiposity through 4 years. This associations might change over time. METHODS: Among 1091 mother-child pairs in a New York City birth cohort study, we measured maternal urinary concentrations of bisphenols and phthalates at three time points in pregnancy and child weight, height, and triceps and subscapular skinfold thickness at ages 1, 2, 3, and 4 years. We used linear mixed models to assess associations of prenatal individual and grouped bisphenols and phthalates with overall and time-point-specific adiposity outcomes from birth to 4 years. RESULTS: We observed associations of higher maternal urinary second trimester total bisphenol and bisphenol A concentrations in pregnancy and overall child weight between birth and 4 years only (Beta 0.10 (95 % confidence interval 0.04, 0.16) and 0.07 (0.02, 0.12) standard deviation score (SDS) change in weight per natural log increase in exposure), We reported an interaction of the exposures with time, and analysis showed associations of higher pregnancy-averaged mono-(2-carboxymethyl) phthalate with higher child weight at 3 years (0.14 (0.06, 0.22)), and of higher high-molecular-weight phthalate, di-2-ethylhexyl phthalate, mono-(2-ethyl-5-carboxypentyl) phthalate, mono-(2-carboxymethyl) phthalate, and mono-(2-ethylhexyl) phthalate with higher child weight at 4 years (0.16 (0.04, 0.28), 0.15 (0.03, 0.27), 0.19 (0.07, 0.31), 0.16 (0.07, 0.24), 0.11 (0.03, 0.19)). Higher pregnancy-averaged high-molecular-weight phthalate, di-2-ethylhexyl phthalate, mono-(2-ethyl-5-carboxypentyl) phthalate, mono-(2-ethyl-5-hydroxyhexyl) phthalate, and mono-2(ethyl-5-oxohexyl) phthalate concentrations were associated with higher child BMI at 4 years (0.20 (0.05, 0.35), 0.20 (0.05, 0.35), 0.22 (0.06, 0.37), 0.20 (0.05, 0.34), 0.20 (0.05, 0.34)). For skinfold thicknesses, we observed no associations. DISCUSSION: This study contributes to the evidence suggesting associations of prenatal exposure to bisphenols and high-molecular-weight phthalates on childhood weight and BMI.

Bridging Differences in Cohort Analyses of the Relationship between Secondhand Smoke Exposure during Pregnancy and Birth Weight: The Transportability Framework in the ECHO Program.

BACKGROUND: Estimates for the effects of environmental exposures on health outcomes, including secondhand smoke (SHS) exposure, often present considerable variability across studies. Knowledge of the reasons behind these differences can aid our understanding of effects in specific populations as well as inform practices of combining data from multiple studies. OBJECTIVES: This study aimed to assess the presence of effect modification by measured sociodemographic characteristics on the effect of SHS exposure during pregnancy on birth weights that may drive differences observed across cohorts. We also aimed to quantify the extent to which differences in the cohort mean effects observed across cohorts in the Environmental influences on Child Health Outcomes (ECHO) consortium are due to differing distributions of these characteristics. METHODS: We assessed the presence of effect modification and transportability of effect estimates across five ECHO cohorts in a total of 6,771 mother-offspring dyads. We assessed the presence of effect modification via gradient boosting of regression trees based on the H-statistic. We estimated individual cohort effects using linear models and targeted maximum likelihood estimation (TMLE). We then estimated transported effects from one cohort to each of the remaining cohorts using a robust nonparametric estimation approach relying on TMLE estimators and compared them to the original effect estimates for these cohorts. RESULTS: Observed effect estimates varied across the five cohorts, ranging from significantly lower birth weight associated with exposure [-167.3g; 95% confidence interval (CI): -270.4, -64.1] to higher birth weight with wide CIs, including the null (42.4g; 95% CI: -15.0, 99.8). Transported effect estimates only minimally explained differences in the point estimates for two out of the four cohort pairs. DISCUSSION: Our findings of weak to moderate evidence of effect modification and transportability indicate that unmeasured individual-level and contextual factors and sources of bias may be responsible for differences in the effect estimates observed across ECHO cohorts. https://doi.org/10.1289/EHP13961.

A randomized, placebo-controlled crossover trial to assess the influence of body weight on aspirin-triggered specialized pro-resolving mediators: Protocol for the DISCOVER Study.

Background: Low-dose aspirin is ineffective for primary prevention of cardiovascular events in people with body weight greater than 70kg. While the prevalent explanation for this is reduced platelet cyclooxygenase-1 (COX-1) inhibition at higher body weights, supporting data are limited, thereby demanding further investigation of the reason(s) underlying this observation. We propose that aspirin-mediated cyclooxygenase-2 (COX-2) acetylation and the resulting synthesis of 15-epi-lipoxin A4, a specialized pro-resolving mediator, is suboptimal in higher weight individuals, which may contribute to the clinical trial findings. Methods: To test this hypothesis, we are conducting a double-blind, placebo-controlled, randomized, mechanistic crossover trial. Healthy men and women exhibiting a wide range of body weights take 81mg aspirin and 325mg aspirin for 3 weeks each, following 3-week placebo run-in and wash-out phases. Our target sample size is 90 subjects, with a minimum of 72 completing all visits estimated to be necessary to achieve power adequate to test our primary hypothesis. Results: Our primary endpoint is the difference in change in plasma 15-epi-lipoxin A4 occurring with each dose of aspirin. Secondary endpoints include lipid mediator profiles, serum bioactive lipid profiles, and other endpoints involved in the resolution of vascular inflammation. Conclusions: Study enrollment began in November 2021 and is ongoing. The results of this study will improve our understanding of the mechanisms underlying aspirin's role(s) in the prevention of adverse cardiovascular outcomes. They may also lead to additional studies with the potential to inform dosing strategies for patients based on body weight.

Exposure to organophosphate esters and maternal-child health.

Organophosphate esters (OPEs) are a class of chemicals now widely used as flame retardants and plasticizers after the phase-out of polybrominated diphenyl ethers (PBDEs). However, OPEs carry their own risk of developmental toxicity, which poses concern for recent birth cohorts as they have become ubiquitous in the environment. In this review, we summarize the literature evaluating the association between OPE exposure and maternal, perinatal, and child health outcomes. We included original articles investigating associations of OPE exposure with any health outcome on pregnant women, newborns, children, and adolescents. We found 48 articles on this topic. Of these, five addressed maternal health and pregnancy outcomes, 24 evaluated prenatal OPE exposure and child health, 18 evaluated childhood OPE exposure and child/adolescent health, and one article evaluated both prenatal and childhood OPE exposure. These studies suggest that OPE exposure is possibly associated with a wide range of adverse health outcomes, including pregnancy loss, altered gestational duration and smaller birthweight, maternal and neonatal thyroid dysfunction, child metabolic dysregulation and abnormal growth, impaired neurodevelopment, and changes in immune response. Many of the reported outcomes associated with OPE exposure varied by child sex. Findings also varied substantially by OPE metabolite and exposure time. The OPEs most frequently measured, detected, and found to be associated with health outcomes were triphenyl phosphate (TPHP, metabolized to DPHP) and tris(1,3-dichloro-2-propyl) phosphate (TDCIPP, metabolized to BDCIPP). The extensive range of health outcomes associated with OPEs raises concern about their growing use in consumer products; however, these findings should be interpreted considering the limitations of these epidemiological studies, such as possible exposure misclassification, lack of generalizability, insufficient adjustment for covariates, and failure to consider chemical exposures as a mixture.

Environmental Exposures and Pediatric Cardiology: A Scientific Statement From the American Heart Association.

Environmental toxicants and pollutants are causes of adverse health consequences, including well-established associations between environmental exposures and cardiovascular diseases. Environmental degradation is widely prevalent and has a long latency period between exposure and health outcome, potentially placing a large number of individuals at risk of these health consequences. Emerging evidence suggests that environmental exposures in early life may be key risk factors for cardiovascular conditions across the life span. Children are a particularly sensitive population for the detrimental effects of environmental toxicants and pollutants given the long-term cumulative effects of early-life exposures on health outcomes, including congenital heart disease, acquired cardiac diseases, and accumulation of cardiovascular disease risk factors. This scientific statement highlights representative examples for each of these cardiovascular disease subtypes and their determinants, focusing specifically on the associations between climate change and congenital heart disease, airborne particulate matter and Kawasaki disease, blood lead levels and blood pressure, and endocrine-disrupting chemicals with cardiometabolic risk factors. Because children are particularly dependent on their caregivers to address their health concerns, this scientific statement highlights the need for clinicians, research scientists, and policymakers to focus more on the linkages of environmental exposures with cardiovascular conditions in children and adolescents.

Organic Pollutant Exposure and CKD: A Chronic Renal Insufficiency Cohort Pilot Study.

Rationale & Objective: This study aimed to assess the effect of exposure to organic pollutants in adults with chronic kidney disease (CKD). Study Design: This was a cross-sectional and longitudinal analysis. Setting and Participants: Forty adults enrolled in the Chronic Renal Insufficiency Cohort (CRIC). Exposures: Exposure at baseline and longitudinally to various organic chemical pollutants. Outcomes: The outcomes were as follows: death; composite of congestive heart failure, myocardial infarction, and stroke; event-free survival from kidney failure or ≥50% decline in estimated glomerular filtration rate (eGFR); and longitudinal trajectory of eGFR. Analytical Approach: We used high-performance liquid chromatography with tandem mass spectrometry to measure urinary concentrations of bisphenols, phthalates, organophosphate pesticides, polycyclic aromatic hydrocarbons, melamine, and cyanuric acid at years 1, 3, and 5 after enrollment in the CRIC. Univariate and multivariable logistic regression were used to examine the association of individual compounds and classes of pollutants with the outcomes. The Cox proportional hazards model and Kaplan-Meier method were used to calculate hazard ratios and 95% CIs for each class of pollutants. Results: Median baseline eGFR and urinary protein-to-creatinine ratio were 33 mL/min/1.73 m2 and 0.58 mg/g, respectively. Of 52 compounds assayed, 30 were detectable in ≥50% of participants. Urinary chemical concentrations were comparable in patients with CKD and healthy individuals from contemporaneous National Health and Nutrition Examination Survey cohorts. Phthalates were the only class with a trend toward higher exposure in patients with CKD. There was an inverse relationship between exposure and the eGFR slopes for bisphenol F, mono-(3-carboxypropyl) phthalate, mono-benzyl phthalate, mono-[2-(carboxymethyl)hexyl] phthalate, and melamine. There were no associations between organic pollutant exposure and cardiovascular outcomes. Limitations: Small sample size, evaluation of single rather than combined exposures. Conclusions: Simultaneous measurement of multiple organic pollutants in adults with CKD is feasible. Exposure levels are comparable with healthy individuals. Select contaminants, especially in the phthalate class, may be associated with more rapid deterioration in kidney function.

The effect of exposure to organic pollutants has not been studied in adults with chronic kidney disease. (CKD). To fill this gap, we measured the exposure to a wide range of chemicals that are found in plastics, personal care products, and food preparation. Overall, the exposure was similar to that noted in the healthy population living in the United States. Only select compounds, mainly phthalates, demonstrated a trend with a more rapid decline in kidney function. These findings provide a useful reference for future studies that aim to evaluate organic pollutant exposure in patients with CKD. This is significant because these exposures represent a modifiable risk factor for disease progression through alterations in diet or lifestyle.