Tertile Of Exposure Research Articles

Prenatal exposure to Nitrogen Oxides and Waist-to-Height Ratio (WHtR) as a cardiovascular risk factor in school-aged children participants of the POSGRAD Cohort

Prenatal exposure to Nitrogen Oxides and Waist-to-Height Ratio (WHtR) as a cardiovascular risk factor in school-aged children participants of the POSGRAD Cohort. Priscila Ceja Esparza¹, Albino Barraza Villarreal¹, Leticia Hernández Cadena¹ ¹ Department of Environmental Health, The National Institute of Public Health of Mexico (INSP) Background and Aim: Prenatal exposure to NOx may increase the risk of obesity and cardiovascular risk factors in children. This study aims to evaluate the relationship between prenatal exposure to NOx and its effect on the behavior of the WHtR in school-aged children from the ages of 7 to 12 years old and to determine if the prenatal supplementation with docosahexaenoic acid (DHA) influences the outcome. Methods: We included 642 mother-child from the POSGRAD cohort. Land use regression models were performed to estimate exposure to NOx (NO, NO2 and NOx) using the results of passive outdoor monitoring from a representative sample of participant households. Child anthropometrics were taken yearly and WHtR was calculated. The association between prenatal exposure to NOx and WHtR was measured through a logistic random-effects model by tertiles of exposure and considering the prenatal supplementation status. Results: We found a significant difference in the risk of having a WHtR >= 0.5, on the second tertile of exposure for NOx between the supplemented (OR= 0.59, IC 95%: 0.10-3.49, p = 0.56) and placebo (OR=13.74, IC 95%: 1.94-97.24, p=0.01) groups when compared with the lowest tertile; in the third tertile the ORs were bigger for both groups, however, these were not significant. Conclusions: Prenatal exposure to NOx can affect the WHtR outcome in children and prenatal supplementation with DHA can decrease this effect. The lack of protection of DHA at higher levels of exposure could suggest a need for higher doses of supplementation. Key Words: Prenatal, Waist-to-Height Ratio, Nitrogen Oxides, Cardiovascular Risk

Serum half-life of PFOA after end of exposure: a highly exposed community in the Veneto Region

Background and aim. Perfluoroalkyl substances (PFAS) are widely used, ubiquitous and highly persistent man-made chemicals. Groundwater of a vast area of the Veneto Region (North-Eastern Italy) was found to be contaminated by PFAS from a manufacturing plant active since the late 1960s. As a result, residents were exposed to PFAS through drinking water until autumn 2013. The aim of the present study was to estimate the decline rates in serum PFAS, and their corresponding serum half-lives, while characterizing their determinants. Methods. The population investigated in this study is a subgroup of the Regional health surveillance program target population consisting of subjects who enrolled in the second surveillance wave (n=2,619). The two blood samples were collected between January 2017 and December 2021. Four of the twelve measured PFAS were detected in greater than 50% of participants: PFOA (100%), PFOS (99.89%), PFHxS (99.01%) and PFNA (61.82%). Serum PFAS excretion rates and half-lives were estimated based on linear mixed effect models, adjusting for a set of contributing factors on PFAS pharmacokinetics such as age, sex, BMI, smoke-habit and eGFR. Results. Median initial serum concentrations were 62.6 ng/mL for PFOA, (range:0.6-1064), 4.6 ng/mL (range:0.5-142) for PFOS, 4.9 ng/mL (range:0.5-109.2) for PFHxS and, 0.6 (range:0.5-0.8) PFNA, with median declines of 61.18%, 36.96%, 40.82% and 41.67%, respectively. The median estimated PFOA’s half-life was 2.90 years (95%CI:2.83-2.95). We found suggestive evidence that half-lives varied when stratified by gender and tertile of exposure, with more rapid elimination in men and higher tertiles of exposure. Conclusions. Drinking water was the dominant route of exposure for PFOA so this study, the largest on PFOA half-life, offers great potential for studying interactions and risk modifications. Other PFAS longer half-lives than reported in other studies might be due to ongoing exposure to PFAS via other routes. Keywords. perfluoroalkyl substances; contaminated water; half-life.

Association of aldehyde exposure with bone mineral density in the national health and nutrition examination survey (NHANES 2013-2014).

The association between aldehyde exposure and bone health in humans remains unclear. This study was to evaluate the association of serum aldehydes with bone mineral density (BMD) and osteopenia/osteoporosis. We analyzed the US National Health and Nutrition Examination Survey cross-sectional data from 2013 to 2014. Weighted multivariate-adjusted linear regression and logistic regression models were used to assess the association between specific aldehydes and osteopenia/osteoporosis. Associations between aldehyde combinations and BMD were also evaluated using the restricted cubic spline (RCS) method. Compared with men in the first tertile, those in the third tertile of propanaldehyde concentration were negatively associated with proximal femur and lumbar spine BMD. Significant inverse associations were observed between benzaldehyde exposure and trochanter BMD in women. Benzaldehyde increased the risk of osteopenia/osteoporosis 2.75-fold [95% confidence interval (CI) = 1.06, 7.11] in the highest tertile in women compared to the lowest tertile concentration. In males, the prevalence of total femur, femur neck, and trochanter osteopenia/osteoporosis was significantly higher in the highest versus the lowest tertile of propanaldehyde exposure, with odds ratios (ORs) of 6.84 (95% CI = 2.33, 20.04), 2.72 (95% CI = 1.18, 6.27), and 3.26 (95% CI = 1.25, 8.56), respectively. RCS regression also showed decreased BMD continuously with increasing serum mixed aldehyde levels. Serum aldehyde concentrations were associated with low BMD and high osteopenia/osteoporosis risk in adults, with propanaldehyde and benzaldehyde being the most critical. Co-exposure to aldehyde combinations was negatively correlated with BMD.

Dialysis Duration and Glucose Exposure Amount Do Not Increase Mortality Risk in Peritoneal Dialysis Patients: A Population-Based Cohort Study From 2004 to 2012.

BackgroundAlthough the bio-incompatibility of glucose-based peritoneal dialysis (PD) solution is well documented, it is used worldwide. How PD duration and the amount of dialyzate glucose exposure affect survival in patients with end-stage renal disease remain inconclusive due to improper study designs in the extant literature.MethodsAll incident patients with PD from 2004 to 2007 who were older than 18 years in Taiwan were included. Patients were censored when they received a transplant or at the end of 2012. Glucose exposure through PD solution was calculated by the mean glucose contained per liter when receiving PD. For those who had already shifted to hemodialysis (HD) and survived longer than 2, 3, and 4 years (the index dates), the cause-specific Cox regression model was used to make the survival comparison by PD duration and mean glucose concentration in these three cohorts, respectively. The model was adjusted by demographics, case-mix, time cohort (2004–2005 vs. 2006–2007), peritonitis episode (none vs. ≥once), and mean PD solution glucose exposure (tertile).ResultsA total of 3,226 patients were included, with a mean age of 53.4 ± 15.2 years, 44.6% being male, and 34.2% having diabetes mellitus. The 1, 2, 3, and 4-year survival rates were 94, 87, 80, and 74%, while technical survival rates were 86, 70, 56, and 45%, respectively. The overall transplant events were 309 (9.6%) only. There were 389, 495, and 553 incident patients with PD shifting to HD included in 2-, 3-, and 4-year cohort, respectively. The population with moderate glucose concentration exposure had the highest mortality, and the high glucose concentration exposure had non-significant lower mortality in each cohort. In various fixed time-window cohorts, the duration of PD treatment did not increase mortality risk after adjustments. In addition, glucose exposure did not affect the mortality rate.ConclusionFor incident PD patients with PD duration no longer than 4 years, neither PD duration nor glucose exposure amount increases the long-term mortality risk.

Association of Habitual Physical Activity With the Risk of All-Cause Mortality Among Chinese Adults: A Prospective Cohort Study.

ObjectiveThis study was conducted to evaluate the association of the risk of all-cause mortality with habitual physical activity (HPA) and its different domains among Chinese adults.MethodsA total of 11,994 participants from the Guangzhou Heart Study were followed up until 1 January 2020. Information on HPA, including leisure-time physical activity (LTPA) and commute activity, was collected using a modified Global Physical Activity Questionnaire. Individual cause of death was obtained from the National Death Registry of China. Cox proportional hazards regression model was used to estimate hazard ratio (HR) and 95% confidence interval (CI) after adjustment for covariates.ResultsDuring 37,715 person-years of follow-up, 208 deaths (1.73%) were observed. When compared with the highest with the lowest exposure tertiles, HPA and LTPA were associated with 34% (HR: 0.66, 95% CI: 0.46–0.95) and 30% (HR: 0.70, 95% CI: 0.49–0.99) reduced risk of all-cause mortality after adjustment for covariates. Commute activity was not associated with mortality risk. For the specific component of LTPA, we found that every 1 MET-h/week increment of the housework was associated with a 1% (HR: 0.99, 95% CI: 0.98–0.99) decreased mortality risk, and performing brisk walking/health exercises/Yangko was associated with a 46% reduced mortality risk (HR: 0.54, 95% CI: 0.29–0.99).ConclusionThis study suggests that a higher level of HPA and LTPA was associated with a lower risk of all-cause mortality. Our findings suggest people to perform HPA, especially LTPA, as a strategy for mortality reduction and health promotion.

Abstract 225: A nested case-control study of untargeted serum protein adductomics and the risk of AML

Abstract Background: A common pathway where carcinogenic chemicals exert their biological influence is the generation of oxidative stress resulting from the production of reactive electrophiles. These electrophiles often form adducts with nucleophilic Cys34 of human serum albumin, which can be quantified to assess in vivo oxidative stress and other biological processes. Here, we aimed to examine the associations of Cys34 albumin adducts with acute myeloid leukemia (AML), the most common adult myeloid leukemia, which has strong links with exposure to certain chemicals and ionizing radiation. Methods: This nested case-control study included data from 52 incident AML cases and 103 controls matched on age, sex, and race from two prospective cohorts: the CLUE study (24 cases and 48 controls) and the PLCO Trial (28 cases and 55 controls) and 42 untargeted serum Cys34 albumin adducts measured by liquid chromatography-high resolution mass spectrometry. We calculated odds ratios (OR) and 95% confidence intervals (CI) for AML risk for each albumin adduct on a continuous scale and across tertiles of exposure in combined samples as well as stratified by the median years of follow-up. Results: The median (range) follow-up from phlebotomy at enrollment was 5.47 (1.02 - 29.93) years. Several Cys34 albumin adducts were significantly associated with incident AML risk. For example, higher serum levels of S-γ-Glu-Cys adduct (894.44) were associated with lower risk of AML (ORcontinuous= 0.18; 95% CI: 0.37-0.92; p-value= 0.04). Similarly, the ORs for the 2nd and 3rd tertiles of adduct levels compared to the lowest tertile were 0.65 (95% CI: 0.31-1.36) and 0.31 (95% CI: 0.12-0.80), respectively (p-trend = 0.01). Stratification by median years of follow-up showed that the association was largely driven by effects present among cases diagnosed ≥5.47 years of follow-up; the ORcontinuous was 0.06 (95% CI: 0.01-0.61; p-value = 0.02) and ORs by tertile were 0.32 (95% CI: 0.09-1.16) and 0.22 (95% CI: 0.06-0.89) for the 2nd and 3rd tertiles, respectively compared to the lowest tertile (p-trend= 0.04). In contrast, there was no association for cases diagnosed within 5.47 years of follow-up (ORcontinuous= 0.78; 95% CI: 0.07-8.95; p-value= 0.84). Conclusion: Higher serum levels of Cys34 adduct of S-γ-Glu-Cys, which is a substrate for the biosynthesis of L-glutathione, a key antioxidant in humans, were associated with a lower risk of AML. Modified Cys34 adducts of human serum albumin could potentially help to understand the underlying mechanisms of leukemogenesis. Citation Format: Mohammad L. Rahman, Bryan Bassig, Hasmik Grigoryan, Wei Hu, Dean Hosgood, Wen-Yi Huang, Jason Wong, Paul Strickland, Stephen Rappaport, Qing Lan, Nathaniel Rothman. A nested case-control study of untargeted serum protein adductomics and the risk of AML [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 225.

Abstract 1443: Environmental heavy metal toxicity and mammographic breast density in a Mississippi Delta southern state

Abstract Importance: Increased mammographic density (MD) is a strong independent risk factor for breast carcinoma. Ubiquitous environmental heavy metal (HM) exposure/toxicity appears pro-carcinogenic in several human cancers. However, studies in the current scientific literature have not elucidated specific connections between HM exposure and mammographically detected increases in breast density. Objective: To determine whether increases in heavy metals (ie, chromium, arsenic and cadmium) measured in urine as a biomarker for long-term exposure, associate with increased MD in a female study cohort in Arkansas. Design, Setting, Participants: One hundred thirty-nine participants in the Arkansas Rural Community Health (ARCH) study cohort, recruited through a mobile mammography unit at baseline, were included in this pilot study. Demographic/health history questionnaire data, urine, blood and saliva samples and incident mammograms classified by BI-RADS were ascertained after informed consent. Study protocol was approved by the Institutional Review Board at the University of Arkansas for Medical Sciences (UAMS). Main Outcome and Measures: Urinary chromium, arsenic and cadmium levels were determined using inductively coupled plasma mass spectrometry. The concentrations of HM were adjusted for urinary creatinine and specific gravity and the results categorized into tertiles. Multivariable logistic regression models were used to evaluate the association between HM exposure and MD. Association of both continuous and categorical variables were examined. Confounding variables in the multivariable models including age, race, BMI, age at menarche and smoking history were determined by a priori knowledge and statistical assessment. Results: Odds ratios (OR) and 95% confidence intervals (CI) for the association between each tertile of HM exposure and MD were used for the assessment. For the unadjusted model, increasing ORs for MD were noted with increased levels of both Chromium and Arsenic exposure. Increased ORs for MD were observed with increased levels of Chromium, Arsenic and Cadmium exposure in the multivariable adjusted model. However, none of these associations demonstrated statistical significance in this limited pilot study. Conclusion: Positive associations between HM exposure and MD were noted after adjusting for age, sex, BMI, age at menarche and smoking history in this pilot study. However, the association did not reach statistical significance at α = 0.05. Citation Format: Bobbie Dean Fine, Shelbie Stahr, Lora J. Rogers, Gail A. Runnells, Tung-Chin Chiang, Lihchyun J. Su. Environmental heavy metal toxicity and mammographic breast density in a Mississippi Delta southern state [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1443.

Pre-pregnancy exposure to arsenic in diet and non-cardiac birth defects.

To explore associations between maternal pre-pregnancy exposure to arsenic in diet and non-cardiac birth defects. This is a population-based, case-control study using maternal responses to a dietary assessment and published arsenic concentration estimates in food items to calculate average daily total and inorganic arsenic exposure during the year before pregnancy. Assigning tertiles of total and inorganic arsenic exposure, logistic regression analysis was used to estimate OR for middle and high tertiles, compared to the low tertile. US National Birth Defects Prevention Study, 1997-2011. Mothers of 10 446 children without birth defects and 14 408 children diagnosed with a non-cardiac birth defect. Maternal exposure to total dietary arsenic in the middle and high tertiles was associated with a threefold increase in cloacal exstrophy, with weak positive associations (1·2-1·5) observed either in both tertiles (intercalary limb deficiency) or the high tertile only (encephalocele, glaucoma/anterior chamber defects and bladder exstrophy). Maternal exposure to inorganic arsenic showed mostly weak, positive associations in both tertiles (colonic atresia/stenosis, oesophageal atresia, bilateral renal agenesis/hypoplasia, hypospadias, cloacal exstrophy and gastroschisis), or the high (glaucoma/anterior chamber defects, choanal atresia and intestinal atresia stenosis) or middle (encephalocele, intercalary limb deficiency and transverse limb deficiency) tertiles only. The remaining associations estimated were near the null or inverse. This exploration of arsenic in diet and non-cardiac birth defects produced several positive, but mostly weak associations. Limitations in exposure assessment may have resulted in exposure misclassification. Continued research with improved exposure assessment is recommended to identify if these associations are true signals or chance findings.

Propensity Score Matching to Determine the Impact of Metformin on All-Cause Mortality in Older Veterans with Diabetes Mellitus.

To determine whether metformin is associated with reduced all-cause mortality in older adults with diabetes mellitus as compared with insulin or sulfonylureas, and to evaluate whether the metformin cumulative exposure followed a dose-response relation. Retrospective cohort study with propensity score matching in veterans 65 years old and older with diabetes mellitus. Patients who had new prescriptions for metformin were matched for demographic and clinical factors with patients receiving new prescriptions for insulin or sulfonylureas using propensity score matching. All-cause mortality risks were compared between metformin and insulin/sulfonylureas using multivariate Cox regression models. A similar approach was used for tertiles of cumulative metformin doses. A sample of 174 veterans taking metformin was matched with 174 who took insulin/sulfonylureas. Most patients were men (97.4%), White (80.45%), and their mean ± standard deviation age was 69.15 ± 7.65 years. Metformin exposure was associated with reduced risk of all-cause mortality (hazard ratio 0.57, 95% confidence interval 0.39-0.84, P = 0.005). The upper tertile of cumulative metformin exposure was associated with lower all-cause mortality in the fully adjusted model (hazard ratio 0.28, 95% confidence interval 0.10-0.77, P = 0.013). This propensity matching study shows that metformin exposure is associated with a lower risk of all-cause mortality. Higher metformin cumulative exposure seems to reduce the risk of all-cause mortality in older veterans with diabetes mellitus.

Association between maternal per- and polyfluoroalkyl substance exposure and newborn telomere length: Effect modification by birth seasons.

Telomere length (TL) is an important biomarker of biological aging and disease that may be affected by prenatal exposure to environmental pollutants. Birth seasons have been linked to reproductive and immune-related diseases. Prenatal exposure to per- and polyfluoroalkyl substance (PFAS) has been associated with adverse birth outcomes, but the effects of PFAS and birth seasons on newborn TL are poorly understood. To explore the individual and combined effects of maternal PFAS exposure on newborn TL, with exploration of the interaction between PFAS and birth seasons on newborn TL. Between June 2015 and May 2018, a total of 499 mother-newborn pairs were recruited for a birth cohort study in Guangxi, China. Maternal blood samples were collected during pregnancy. Nine PFASs were measured by ultraperformance liquid chromatography-mass spectrometry. Newborn TL was assessed using quantitative real-time polymerase chain reaction. Modeling newborn TL as the outcome, multivariable linear regressions were performed for individual PFAS exposures, and Bayesian Kernel Machine Regressions were performed for PFAS mixtures. Furthermore, interaction analyses were conducted to evaluate the effect modification by birth seasons in these relationships. For both single and multipollutant models, PFASs exposure were inversely associated with newborn TL, although none of the relationships were significant. The mixture of PFASs showed a potential positive trend of combined effect on newborn TL but non-statistically significant. Each ln-transformed unit concentration increase in PFOA was related to a 20.41% (95% CI: -30.44%, -8.93%) shorter TL in spring-born infants but not in those born in other birth seasons. Mothers in the middle and highest tertiles of PFOA exposure had 11.69% and 10.71% shorter TLs in spring-born infants, respectively. Maternal PFAS exposure showed little association with newborn TL. The results suggested potential effect modification by birth season on the association between PFOA exposure and newborn TL.

Fine particulate matter and polycystic ovarian morphology

BackgroundPolycystic ovary morphology (PCOM) is an ultrasonographic finding that can be present in women with ovulatory disorder and oligomenorrhea due to hypothalamic, pituitary, and ovarian dysfunction. While air pollution has emerged as a possible disrupter of hormone homeostasis, limited research has been conducted on the association between air pollution and PCOM.MethodsWe conducted a longitudinal cohort study using electronic medical records data of 5,492 women with normal ovaries at the first ultrasound that underwent a repeated pelvic ultrasound examination during the study period (2004–2016) at Boston Medical Center. Machine learning text algorithms classified PCOM by ultrasound. We used geocoded home address to determine the ambient annual average PM2.5 exposures and categorized into tertiles of exposure. We used Cox Proportional Hazards models on complete data (n = 3,994), adjusting for covariates, and additionally stratified by race/ethnicity and body mass index (BMI).ResultsCumulative exposure to PM2.5 during the study ranged from 4.9 to 17.5 µg/m3 (mean = 10.0 μg/m3). On average, women were 31 years old and 58% were Black/African American. Hazard ratios and 95% confidence intervals (CI) comparing the second and third PM2.5 exposure tertile vs. the reference tertile were 1.12 (0.88, 1.43) and 0.89 (0.62, 1.28), respectively. No appreciable differences were observed across race/ethnicity. Among women with BMI ≥ 30 kg/m2, we observed weak inverse associations with PCOM for the second (HR: 0.93, 95% CI: 0.66, 1.33) and third tertiles (HR: 0.89, 95% CI: 0.50, 1.57).ConclusionsIn this study of reproductive-aged women, we observed little association between PM2.5 concentrations and PCOM incidence. No dose response relationships were observed nor were estimates appreciably different across race/ethnicity within this clinically sourced cohort.

Pregnancy exposure to bisphenol A and duration of breastfeeding

IntroductionBisphenol A (BPA) is frequently used in the production of plastics. It is an endocrine disruptor, and BPA exposure in mice has been associated with reduced offspring growth due to insufficient milk production. However, human studies of associations between BPA exposure and duration of breastfeeding are sparse. MethodsPregnant women from the Odense Child Cohort (n = 725) donated a third trimester morning urine sample, which was analyzed for BPA by LC-MS/MS. Information about duration of exclusive and any breastfeeding was obtained through questionnaires three and 18 months postpartum, and a subgroup of women responded to weekly text messages about breastfeeding. Associations between pregnancy BPA exposure and duration of breastfeeding were analyzed using Cox regression adjusting for potential confounders. ResultsThe median urine BPA concentration was 1.29 ng/mL. Compared to women within the lowest tertile of BPA exposure, women in the second and third tertile were slightly more likely to terminate breastfeeding at any given time; HRs (95% CI) were 1.05 (0.87; 1.26) and 1.06 (0.89; 1.27), respectively, and to terminate exclusive breastfeeding at any time up to 20 weeks after birth, HRs (95% CI) were 1.07 (0.88; 1.28) and 1.06 (0.88; 1.27), respectively. However, confidence intervals were also compatible with no effect or even a protective effect. DiscussionThis study indicated that high BPA exposure in pregnancy was associated with shorter duration of breastfeeding. Although our findings were not statistically significant, all estimates were above one suggesting increased risk of early breastfeeding termination with high exposure. Using a single spot morning urine sample to measure BPA has likely caused imprecision as it might not adequately reflect long term exposure. Future studies should consider measuring BPA more than once, including other timepoints during pregnancy and after birth.

Lipidomic biomarkers: Potential mediators of associations between urinary bisphenol A exposure and colorectal cancer

Previous research reported associations between bisphenol A (BPA) exposure and some malignant tumor incidences, yet the underlying mechanism remains largely uncertain. This investigation was aimed to explore the association of BPA exposure burden with colorectal cancer (CRC) and the role of tumor tissue lipid metabolism in the associations between BPA and CRC using lipidomic approach. Urinary BPA levels in CRC cases were significantly higher than those in controls (P value < 0.05). BPA was positively correlated with all three serum CRC biomarkers, with an estimated odds ratio (OR) of 4.45 (95% confidence interval (95% CI): [1.31, 15.14]) between the highest and lowest tertiles of exposure. Lipidomic screening of tumor samples suggested significant perturbation in the glycerophospholipid metabolism pathway, of which phosphatidylcholine (PC 34:0), phosphatidylcholine (PC 37:1), phosphatidylethanolamine (PE 34:2), triacylglycerol (TG 56:4) demonstrated mediation contribution of 21.9%, 18.7%, 18.4% and 27.39%, respectively, in the association between BPA exposure and CRC. Our work provides novel findings that cancer tissue metabolites may be playing vital mediating roles in the associations between BPA exposure burden and CRC risk. These findings contribute to better understanding of the etiology of CRC induced by environmental stressors.

Prenatal maternal pesticide exposure in relation to sleep health of offspring during adolescence

Study objectivesThe neurobiological processes involved in establishing sleep regulation are vulnerable to environmental exposures as early as seven weeks of gestation. Studies have linkedin utero pesticide exposure to childhood sleep-disordered breathing. However, the impact of in utero pesticide exposure on the sleep health of adolescents remains unexplored. Materials and methodsData from 137 mother-adolescent pairs from a Mexico City cohort were analyzed. We used maternal urinary 3-phenoxybenzoic acid (3-PBA, pyrethroid metabolite) and 3, 5, 6-trichloro-2-pyridinol (TCPy, chlorpyrifos metabolite) from trimester three to estimate in utero pesticide exposure. Among adolescents, we obtained repeated measures of objectively assessed sleep duration, midpoint, and fragmentation using wrist-actigraphy devices for 7 consecutive days in 2015 and 2017. Unstratified and sex-stratified associations between maternal urinary 3-PBA and TCPy and adolescent sleep measures were examined using generalized linear mixed models (GLMMs). We also examined the interactive effects of maternal pesticide exposure and offspring sex on sleep outcomes. Results3-PBA and TCPy were detected in 44.4% and 93% of urine samples, respectively. Adjusted findings demonstrated that higher exposure to maternal TCPy was associated with longer sleep duration and later sleep timing. Findings from interaction tests between maternal pesticide exposure and offspring sex were not statistically significant, although adjusted sex-stratified findings showed that the association between TCPy with duration and midpoint was evident only among female offspring. To illustrate, those in the highest tertile of exposure had a 59 minute (95% CI: 12.2, 104.8) (p, trend = 0.004) longer sleep duration and a 0.6 hour (95% CI: 0.01, 1.3) (p, trend = 0.01) later sleep midpoint. We found no significant associations between 3-PBA and sleep outcomes. ConclusionWithin a cohort of mother-adolescent pairs, we found associations between maternal prenatal pesticide exposure and longer sleep duration and later sleep timing among adolescent offspring. Further, this association may be female-specific.

Styrene associated respiratory outcomes among reinforced plastic industry workers

The study aim was to determine whether styrene exposure was associated with respiratory outcomes in a dose-response manner in the fibreglass reinforcement industry. Workers (n=254) from a fibreglass reinforcement factory were subjected to a standardised interview, spirometry and styrene monitoring. Cumulative exposure was calculated across different jobs and levels of exposure. Logistic regression modelling estimated risk for symptoms, respiratory diseases and lung function change across exposure tertiles. The geometric means of styrene in the General Laminating and Fitting Departments were 48.2 mg/m3 (95% CI 36.3–64.1 mg/m3) and 20.7 mg/m3 (95% CI: 15.6–27.5 mg/m3), respectively. The cumulative exposure odds ratios for chronic cough, phlegm, wheezing and breathlessness for high exposure was 3.1 (95% CI 1.1–8.6), 5.3 (95% CI 1.7–16.6), 3.3 (95% CI 1.2–9.1) and 5.5 (95% CI 1.15–26.4), respectively. The cumulative exposure associated reduction in FEV1/FVC ratio, percent predicted FEV1 and FVC was 0.01, 0.04% and 0.05%, respectively. Styrene exposure increases the risk of respiratory symptoms and is associated with reduced lung function.

A pilot study of glyphosate, and preterm birth among blacks and whites

BACKGROUND AND AIM: Glyphosate was first registered as an herbicide in the United States in 1974. It has since been linked to birth defects in animal models. Additionally, in vitro studies suggest that glyphosate has anti-androgenic and anti-estrogenic activities including the ability to interfere with aromatase activity. One observational human study found a statistically significant correlation between higher maternal glyphosate levels and shortened gestational length. However, no studies have investigated potential race-disparities in gestational glyphosate exposure or effects. METHODS: A nested case control pilot study enrolled 26 women with a preterm birth (37 weeks completed gestation) and 26 term births matched by race from a larger cohort study. Second trimester urine samples, collected at 18-22 weeks of gestation, were analyzed for specific-gravity corrected glyphosate using liquid chromatography-tandem mass spectrometry. Logistic regression was used to estimate the association between gestational urinary glyphosate concentrations and preterm birth, adjusted for age, race, body mass index, season of specimen collection, education level and reported organic food consumption. RESULTS:Geometric mean glyphosate concentrations were 0.07 ng/mL (95% CI: 0.04-0.13) for preterm and 0.06 ng/mL for term births (95% CI: 0.03-0.10). Fewer term whites (n=4, 31%) were in the middle (range: 0.04-0.11 ng/mL) and highest (range: 0.17-1.25 ng/mL) tertiles of glyphosate exposure than term Blacks (n=7, 54%), although the difference was not statistically significant (p=0.43). Higher urinary glyphosate was associated with lower odds of preterm birth (odds ratio=0.75, 95% confidence interval 0.16-3.68), adjusted for covariates, although also not statistically significant. The odds varied by race, with OR=0.60 (95% CI: 0.11-3.4) among whites and OR=1.40 (95% CI: 0.28-7.02) among Blacks, although the interaction was not statistically significant. CONCLUSIONS:Glyphosate exposure varied by maternal race with elevated exposure in Blacks. There was no association found between urinary glyphosate levels and preterm birth, suggesting that glyphosate may not be a preterm birth risk factor. KEYWORDS: Glyphosate, Pregnancy Outcomes, Risk Assessment, Exposure assessment-biomarkers of exposure

Prenatal Exposure to Perfluoroalkyl Substances and Mental Health in Childhood

BACKGROUND AND AIM: Epidemiological studies have evaluated the effect of prenatal exposure to perfluoroalkyl substances (PFAS) on neurobehavioral and cognitive endpoints in childhood, but a research focus on mental health is lacking. We evaluated the associations between prenatal PFAS exposure and mental health including depressive symptoms, physical or emotional stress, and psychosis-like experience in children at age 11. METHODS: Using pooled samples in the Danish National Birth Cohort established between 1996 and 2002 (N=2,250), we estimated the associations between concentrations of six types of PFAS in maternal plasma (median, 8 gestational weeks) and child self-report mental health outcomes using validated questionnaires. Binary classifications (with or without moderate/severe symptoms) for each of the outcomes and continuous outcome variables were analyzed. We used unconditional logistic regressions to estimate the adjusted odds ratio (OR) and 95% confidence interval (CI) for the binary outcomes according to log2-transformed PFAS concentrations and PFAS tertiles. PFAS mixture by using the weighted-quantile-sum index was conducted. Analyses were repeated using negative binomial regressions for continuous count outcome variables. Sex-specific analyses were conducted. RESULTS:The highest exposure tertile for perfluorooctanoic acid (OR=1.34, 95% CI: 1.06, 1.71), perfluorohexane sulfonate (OR=1.43, 95% CI: 1.06, 1.92) and perfluoroheptane sulfonate (OR=1.37, 95% CI: 1.02, 1.84) were associated with elevated physical or emotional stress in childhood. The WQS index for PFAS mixture was also positively associated with stress in childhood (OR=1.21, 95% CI: 1.05, 1.40). There were no consistent associations found for these PFAS compounds and depressive symptoms or psychosis-like experience. Findings from negative binomial regressions were similar. There were also no apparent differences in analyses stratified by sex. CONCLUSIONS:Higher prenatal levels of three PFAS compounds and PFAS mixtures might influence physical and emotional stress in childhood. More research of fetal exposures to environmental pollutants and mental health risk in the offspring would be needed. KEYWORDS: PFAS, Mental health outcomes, Children's environmental health, Environmental epidemiology

PENTOSAN POLYSULFATE AND VISION: Findings from an International Survey of Exposed Individuals.

To investigate patient-reported visual function among individuals taking pentosan polysulfate (PPS) for interstitial cystitis. A 27-item online survey was distributed to an international mailing list of individuals with interstitial cystitis in November 2018. Demographic characteristics, PPS exposure history, subjective visual function, and previous macular diagnoses were queried. The impact of PPS use, grouped by tertile of cumulative exposure, on visual function and macular diagnoses was assessed with multivariate logistic regression. The survey was completed by 912 respondents. Eight hundred and sixty-one (96.4%) were women, and the median age was 55 [interquartile range (IQR), 45-64 years]. Among PPS users, the median exposure was 547.5 g (IQR, 219-1,314 g). Respondents in the highest PPS exposure tertile were more likely to report difficulty with reading small print [adjusted odds ratio 2.29, 95% confidence interval (CI) 1.15-4.57] and to have a diagnosis of macular degeneration and/or pigmentary maculopathy (adjusted odds ratio 2.41, 95% CI 1.44-4.03) than unexposed respondents. In this large sample of individuals with interstitial cystitis, those in the highest PPS exposure category were more likely to have difficulties reading small print and to report a previous diagnosis of macular disease. Further study of objective measures of visual function in PPS users is warranted.

Ingestion of Nitrate and Nitrite and Risk of Stomach and Other Digestive System Cancers in the Iowa Women's Health Study.

Nitrate and nitrite are precursors in the endogenous formation of N-nitroso compounds (NOC) which are potent animal carcinogens for the organs of the digestive system. We evaluated dietary intakes of nitrate and nitrite, as well as nitrate ingestion from drinking water (public drinking water supplies (PWS)), in relation to the incidence (1986–2014) of cancers of the esophagus (n = 36), stomach (n = 84), small intestine (n = 32), liver (n = 31), gallbladder (n = 66), and bile duct (n = 58) in the Iowa Women’s Health Study (42,000 women aged from 50 to 75 in 1986). Dietary nitrate and nitrite were estimated using a food frequency questionnaire and a database of nitrate and nitrite levels in foods. Historical nitrate measurements from PWS were linked to the enrollment address by duration. We used Cox regression to compute hazard ratios (HR) and 95% confidence intervals (CI) for exposure quartiles (Q), tertiles (T), or medians, depending on the number of cancer cases. In adjusted models, nitrite intake from processed meats was associated with an increased risk of stomach cancer (HRQ4vsQ1 = 2.2, CI: 1.2–4.3). A high intake of total dietary nitrite was inversely associated with gallbladder cancer (HRQ4vsQ1 = 0.3, CI: 0.1–0.96), driven by an inverse association with plant sources of nitrite (HRQ4vsQ1 = 0.3, CI: 0.1–0.9). Additionally, small intestine cancer was inversely associated with a high intake of animal nitrite (HRT3vsT1 = 0.2, CI: 0.1–0.7). There were no other dietary associations. Nitrate concentrations in PWS (average, years ≥ 1/2 the maximum contaminant level) were not associated with cancer incidence. Our findings for stomach cancer are consistent with prior dietary studies, and we are the first to evaluate nitrate and nitrite ingestion for certain gastrointestinal cancers.

Risk of breast cancer and prediagnostic urinary excretion of bisphenol A, triclosan and parabens: The Multiethnic Cohort Study.

Exposure to bisphenol A (BPA), triclosan and parabens is widespread but their impact on breast cancer risk remains unclear. This nested case-control study investigated endocrine-disrupting chemicals (EDCs) and breast cancer risk within the Multiethnic Cohort (MEC). We measured prediagnostic urinary BPA, triclosan and parabens in 1032 postmenopausal women with breast cancer (48 African American, 77 Latino, 155 Native Hawaiian, 478 Japanese American and 274 White) and 1030 individually matched controls, using a sensitive and validated liquid chromatography mass spectrometry assay. Conditional logistic regression was used to examine risk with these EDCs with adjustment for creatinine and potential confounders. In all women, breast cancer risk was not associated with BPA (Ptrend =0.53) and was inversely associated with triclosan (ORT3 vs T1 =0.83, 95% CI: 0.66-1.04, Ptrend =0.045) and total parabens (ORT3 vs T1 =0.77, 95% CI: 0.62-0.97, Ptrend =0.03). While risk of hormone receptor positive (HR+) cancer was 20% to 23% lower among women in the upper two tertiles of paraben exposure (Ptrend =0.02), risk of HR negative (HR-) was reduced 27% but only among those in the upper tertile of exposure. Although risk associations did not differ significantly by ethnicity or by body mass index (BMI), the inverse association with triclosan was observed mainly among overweight/obese women (ORT3 vs T1 =0.76, 95% CI: 0.56-1.02, Ptrend =0.02). In summary, breast cancer risk in a multiethnic population was unrelated to BPA and was weakly inversely associated with triclosan and paraben exposures. Studies with multiple urine samples collected before breast cancer diagnosis are needed to further investigate these EDCs and breast cancer risk.