Associations between follicular fluid trace elements and ovarian response during in vitro fertilization.

INTRODUCTION: Exposure to trace elements has been associated with ovarian response in experimental studies. We conducted a hypothesis-generating study of associations between ovarian follicular fluid (FF) trace elements and measures of ovarian response among women using in vitro fertilization (IVF). METHODS: We collected ovarian FF specimens from 56 women. We determined concentrations (µg/L) of 11 trace elements using inductively coupled plasma-tandem mass spectrometry. We estimated associations between women's FF trace elements per interquartile range difference, and measures of ovarian response using linear (peak estradiol (E2), baseline anti-mullerian hormone (AMH), and follicle stimulating hormone (FSH)) and negative binomial (baseline antral follicle count (AFC) and oocyte count) regression, adjusting for confounding factors. We used principal component analysis (PCA) to estimate the associations of the FF trace elements mixture. We also explored FF oxidative stress enzymes as causal mediators of the associations. RESULTS: Higher FF cobalt was associated with greater peak E2 (mean difference = 351.48 pg/mL; 95%CI: 21.76, 724.71) and AFC (rate ratio = 1.14; 95%CI: 1.01, 1.28), and higher FF copper was associated with greater peak E2 (mean difference = 335.66 pg/mL; 95%CI: 81.77, 753.08) and oocyte count (rate ratio = 1.19; 95%CI: 1.02, 1.43). Higher FF mercury was also associated with greater peak E2 (mean difference = 410.70 pg/mL; 95%CI: 61.90, 883.39). Higher FF lead was associated with lesser AFC (rate ratio = 0.85; 95%CI: 0.73, 0.98). Using PCA, the mixture of Sr, Hg, and As was associated with higher peak estradiol, AFC, and oocyte count. FF glutathione peroxidase, paraoxonase, and arylesterase activities were inconsistent mediators of the associations, but the effect estimates were imprecise. CONCLUSION: Our results suggest that essential and non-essential trace elements in FF were associated with ovarian response during IVF.

Early childhood exposure to environmental phenols and parabens, phthalates, organophosphate pesticides, and trace elements in association with attention deficit hyperactivity disorder (ADHD) symptoms in the CHARGE study.

BACKGROUND: A growing body of literature investigated childhood exposure to environmental chemicals in association with attention-deficit/hyperactivity disorder (ADHD) symptoms, but limited studies considered urinary mixtures of multiple chemical classes. This study examined associations of concurrent exposure to non-persistent chemicals with ADHD symptoms in children diagnosed with autism spectrum disorder (ASD), developmental delay (DD), and typical development (TD). METHODS: A total of 549 children aged 2-5 years from the Childhood Autism Risks from Genetics and Environment (CHARGE) case-control study were administered the Aberrant Behavior Checklist (ABC). This study focused on the ADHD/noncompliance subscale and its two subdomains (hyperactivity/impulsivity, inattention). Sixty-two chemicals from four classes (phenols/parabens, phthalates, organophosphate pesticides, trace elements) were quantified in child urine samples, and 43 chemicals detected in > 70% samples were used to investigate their associations with ADHD symptoms. Negative binomial regression was used for single-chemical analysis, and weighted quantile sum regression with repeated holdout validation was applied for mixture analysis for each chemical class and all chemicals. The mixture analyses were further stratified by diagnostic group. RESULTS: A phthalate metabolite mixture was associated with higher ADHD/noncompliance scores (median count ratio [CR] = 1.10; 2.5th, 97.5th percentile: 1.00, 1.21), especially hyperactivity/impulsivity (median CR = 1.09; 2.5th, 97.5th percentile: 1.00, 1.25). The possible contributors to these mixture effects were di-2-ethylhexyl phthalate (DEHP) metabolites and mono-2-heptyl phthalate (MHPP). These associations were likely driven by children with ASD as these were observed among children with ASD, but not among TD or those with DD. Additionally, among children with ASD, a mixture of all chemicals was associated with ADHD/noncompliance and hyperactivity/impulsivity, and possible contributors were 3,4-dihydroxy benzoic acid, DEHP metabolites, MHPP, mono-n-butyl phthalate, and cadmium. CONCLUSIONS: Early childhood exposure to a phthalate mixture was associated with ADHD symptoms, particularly among children with ASD. While the diverse diagnostic profiles limited generalizability, our findings suggest a potential link between phthalate exposure and the comorbidity of ASD and ADHD.

Early childhood exposure to environmental phenols and parabens, phthalates, organophosphate pesticides, and trace elements in association with attention deficit hyperactivity disorder (ADHD) symptoms in the CHARGE study.

Background: Agrowing body of literature investigated childhood exposure to environmental chemicals in association with attention deficit hyperactivity disorder (ADHD) symptoms, but limited studies considered urinary mixtures of multiple chemical classes. This study examined associations of concurrent exposure to non-persistent chemicals with ADHD symptoms in children diagnosed with autism spectrum disorder (ASD), developmental delay, and typical development. Methods: A total of 574 children aged 2-5 years from the Childhood Autism Risks from Genetics and Environment (CHARGE) case-control study was administered the Aberrant Behavior Checklist (ABC). This study focused on the Hyperactivity subscale and its two subdomains (hyperactivity/impulsivity, inattention). Sixty-two chemicals from four classes (phenols/parabens, phthalates, organophosphate pesticides, trace elements) were quantified in child urine samples, and 43 chemicals detected in >70% samples were used in statistical analyses. Weighted quantile sum regression for negative binomial outcomes with repeated holdout validation was performed to investigate covariate-adjusted associations between mixtures and ABC scores in 574 children. The mixture analyses were further restricted to 232 children with ASD. Results: Phthalate metabolite mixtures, weighted for mono-n-butylphthalate (MNBP), mono-2-heptyl phthalate, and mono-carboxy isononyl phthalate, were associated with the Hyperactivity subscale (mean incidence rate ratio [mIRR] = 1.11; 2.5th, 97.5th percentile: 1.00, 1.23), especially the hyperactivity/impulsivity subdomain (mIRR = 1.14; 2.5th, 97.5th percentile: 1.06, 1.26). These associations remained similar after restricting to children with ASD. The inattention subdomain was associated with a phenols/parabens mixture, weighted for several parabens and bisphenols (mIRR = 1.13; 2.5th, 97.5th percentile: 1.00, 1.28) and a total mixture, weighted for 3,4-dihydroxy benzoic acid, MNBR and mono-(2-ethyl-5-carboxypentyl) phthalate (mIRR = 1.11; 2.5th, 97.5th percentile: 1.01,1.25) only among children with ASD. Conclusions: Concurrent exposure to phthalate mixtures was associated with hyperactivity in early childhood. Though causal inference cannot be made based on our cross-sectional findings, this study warrants further research on mixtures of larger number of chemicals from multiple classes in association with ADHD-related behaviors in young children.

Airborne levels of cadmium are correlated with urinary cadmium concentrations among young children living in the New York state city of Syracuse, USA.

Air pollution is a serious public health issue with early childhood exposure being of high concern because of the greater risk that children might experience negative health outcomes. Industrial sources in and near communities are one potential path of exposure that children might face with greater levels of air pollution correlating with higher levels of toxicants detected in children. We compare estimated ambient air concentrations of Cadmium (Cd) to a cohort (n = 281) of 9 to 11-year old children during their early childhood years (0-5 years of age) in a mid-size city in Upstate New York. Levels of Cd air pollution are compared to children's urine-Cd levels. Urine has been shown to be a superior biomarker to blood for Cd exposure particularly for longer-term exposures. We find that participants who reside in households that faced greater Cd air pollution during the child's early years have higher urine-Cd levels. This association is stable and stronger than previously presented associations for blood-Cd. Findings support expanded use of air modelling data for risk screening to reduce the potential health burden that industrial pollution can have.

Environmental exposures to pesticides, phthalates, phenols and trace elements are associated with neurodevelopment in the CHARGE study.

OBJECTIVE: To determine if higher exposures measured in early childhood to environmental phenols, phthalates, pesticides, and/or trace elements, are associated with increased odds of having a diagnosis of Autism Spectrum Disorder (ASD), Developmental Delay (DD), or Other Early Concerns (OEC) compared to typically developing children (TD). METHODS: This study included 627 children between the ages of 2-5 who participated in the Childhood Autism Risks from Genetics and Environment (CHARGE) study. Urine samples were collected at the same study visit where diagnostic assessments to confirm diagnosis indicated during the recruitment process were performed. Adjusted multinomial regression models of each chemical with diagnosis as the outcome were conducted. Additionally, two methods were used to analyze mixtures: repeated holdout multinomial weighted quantile sum (WQS) regression for each chemical class; and a total urinary mixture effect was assessed with repeated holdout random subset WQS. RESULTS: Many urinary chemicals were associated with increased odds of ASD, DD or OEC compared to TD; however, most did not remain significant after false discovery rate adjustment. Repeated holdout WQS indices provided evidence for associations of both a phenol/paraben mixture effect and a trace element mixture effect on DD independently. In analyses adjusted for confounders and other exposures, results suggested an association of a pesticide mixture effect with increased risk for ASD. Results also suggested associations of a total urinary mixture with greater odds of both ASD and DD separately. CONCLUSION: Higher concentrations of urinary biomarkers were associated with ASD, DD, and OEC compared to TD, with consistency of the results comparing single chemical analyses and mixture analyses. Given that the biospecimens used for chemical analysis were generally collected many months after diagnoses were made, the direction of any causal association is unknown. Hence findings may reflect higher exposures among children with non-typical development than TD children due to differences in behaviors, metabolism, or toxicokinetics.

High Lead Exposure Associated With Higher Blood Pressure in Haiti: a Warning Sign for Low-Income Countries.

Cardiovascular disease is the leading cause of death in lower-income countries including Haiti. Environmental lead exposure is associated with high blood pressure and cardiovascular mortality in high-income countries but has not been systematically measured and evaluated as a potential modifiable cardiovascular risk factor in lower-income countries where 6.5 billion people reside. We hypothesized lead exposure is high in urban Haiti and associated with higher blood pressure levels. Blood lead levels were measured in 2504 participants ≥18 years enrolled in a longitudinal population-based cohort study in Port-au-Prince. Lead screening was conducted using LeadCare II (detection limit ≥3.3 µg/dL). Levels below detection were imputed by dividing the level of detection by √2. Associations between lead (quartiles) and systolic blood pressure and diastolic blood pressure were assessed, adjusting for age, sex, obesity, smoking, alcohol, physical activity, income, and antihypertensive medication use. The median age of participants was 40 years and 60.1% were female. The geometric mean blood lead level was 4.73µg/dL, 71.1% had a detectable lead level and 42.3% had a blood lead level ≥5 µg/dL. After multivariable adjustment, lead levels in quartile four (≥6.5 µg/dL) compared with quartile 1 (<3.4 µg/dL) were associated with 2.42 mm Hg (95% CI, 0.36-4.49) higher systolic blood pressure and 1.96 mm Hg (95% CI, 0.56-3.37) higher diastolic blood pressure. In conclusion, widespread environmental lead exposure is evident in urban Haiti, with higher lead levels associated with higher systolic and diastolic blood pressure. Lead is a current and potentially modifiable pollutant in lower-income countries that warrants urgent public health remediation. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03892265.

Early life blood lead levels and asthma diagnosis at age 4-6 years.

The USA has a high burden of childhood asthma. Previous studies have observed associations between higher blood lead levels and greater hypersensitivity in children. The objective of the present study was to estimate the association between blood lead concentrations during early childhood and an asthma diagnosis between 48 and 72 months of age amongst a cohort with well-characterized blood lead concentrations. Blood lead concentrations were measured at 6, 12, 18, 24, 36, and 48 months of age in 222 children. The presence of an asthma diagnosis between 48 and 72 months was assessed using a questionnaire which asked parents or guardians whether they had been told by a physician, in the past 12 months, that their child had asthma. Crude and adjusted risk ratios (RR) of an asthma diagnosis were estimated for several parameterizations of blood lead exposure including lifetime average (6 to 48 months) and infancy average (6 to 24 months) concentrations. After adjustment for child sex, birthweight, daycare attendance, maternal race, education, parity, breastfeeding, income, and household smoking, age-specific or composite measures of blood lead were not associated with asthma diagnosis by 72 months of age in this cohort.

Toxic elements in follicular fluid adversely influence the likelihood of pregnancy and live birth in women undergoing IVF.

STUDY QUESTION: Are follicular fluid (FF), arsenic (As), mercury (Hg), cadmium (Cd) and lead (Pb) concentrations associated with IVF outcomes among women undergoing IVF? SUMMARY ANSWER: There was a non-linear association between higher FF Hg concentration and a lower likelihood of biochemical pregnancy and live birth. Higher FF Pb concentration was also associated with a lower probability of live birth. WHAT IS KNOWN ALREADY: Previous research suggests that toxic elements may affect fertility among couples conceiving with and without assistance. However, the results have been inconsistent, possibly related in part to exposure misclassification. Very few studies have used ovarian FF to measure toxic elements, as it requires an invasive collection procedure, yet it may offer a more accurate estimate of a biologically effective dose than blood or urine. STUDY DESIGN SIZE DURATION: This is a prospective study of 56 women undergoing IVF, from October 2015 to June 2017. FF was collected for analysis on the day of oocyte retrieval. PARTICIPANTS/MATERIALS SETTING METHODS: As, Cd, Hg and Pb were determined in 197 FF specimens, using inductively coupled plasma tandem mass spectrometry. FF glutathione peroxidase, glutathione reductase, total glutathione-S-transferase, superoxide dismutase, arylesterase and paraoxonase (PON1p) activities were measured using kinetic enzyme assays. MAIN RESULTS AND THE ROLE OF CHANCE: Non-linear associations were detected, in which the probabilities of biochemical pregnancy (P = 0.05) and live birth (P = 0.05) were lower in association with FF Hg greater than ∼0.51 µg/l Hg, adjusted for age, race, cigarette smoking and recent seafood consumption. Higher FF Pb was also associated with a lower likelihood of live birth (relative risk (RR) = 0.68, 95% CI: 0.46, 1.00; P = 0.05). We also found a suggestive, although imprecise, antagonizing mediating effect of PON1p activity on the association between FF Pb and live birth (-28.3%; 95% CI: -358%, 270%). LIMITATIONS REASONS FOR CAUTION: The results should be interpreted judiciously given the limited sample size and difficulty accounting for correlated data in generalized additive models and mediation analyses. Additionally, women undergoing IVF are highly selected with respect to age and socioeconomic status, and so the generalizability of the results may be limited. WIDER IMPLICATIONS OF THE FINDINGS: Overall, the results suggest that FF Hg was associated with a lower likelihood of biochemical pregnancy and live birth, with a potential threshold effect, and that higher FF Pb was associated with a lower probability of live birth. These results may help to guide clinical recommendations for limiting the exposure of patients to Hg and Pb and ultimately improve IVF success rates. STUDY FUNDING/COMPETING INTERESTS: This work was funded in part by the National Institute of Environmental Health Sciences (NIEHS), grant number 1R56ES023886-01, to the University at Albany (M.S.B.), and in part by the National Institute of Environmental Health Sciences (NIEHS), grant number 1U2CES026542-01, to the Wadsworth Center (P.J.P.). The authors declare no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Variability of essential and non-essential trace elements in the follicular fluid of women undergoing in vitro fertilization (IVF).

Both essential and non-essential elements have been associated with female reproductive function in epidemiologic investigations, including among IVF populations. To date, most investigators have used blood or urine to assess biomarkers of exposure, with few employing ovarian follicular fluid (FF). FF may offer a more direct "snapshot" of the oocyte microenvironment than blood or urine, however previous studies report follicle-to-follicle variability in FF constituents that may contribute to exposure misclassification. Our objectives were to investigate sources of trace element variability, to estimate FF biomarker reliability among women undergoing IVF (n = 34), and to determine the minimum number of follicles required to estimate subject-specific mean concentrations. We measured As, Hg, Cd, Pb, Cu, Mn, Se, and Zn in FF samples using inductively coupled plasma tandem mass spectrometry. Inter-subject (between-women) variability contributed most of the variability in FF element concentrations, with ovarian, follicular, and analytical as smaller sources of variability. The proportion of variability attributable to sources between-follicles differed by age, body mass index (BMI), race, and cigarette smoking for Cu, Se, and Zn, by BMI and cigarette smoking for As, by primary infertility diagnosis for Hg, Cu, Se, and Zn, and by ovarian stimulation protocol for Mn and Se. Four to five individual follicles were sufficient to estimate subject-specific mean Cu, Se, and Zn concentrations, while >14 were necessary for As, Hg, Cd, Pb, and Mn. Overall, our results suggest that FF is a suitable source of biomarkers of As and Hg exposure in ovarian follicles. Although limited in size, our study offers the most comprehensive exploration of biological variation in FF trace elements to date and may provide guidance for future studies of ovarian trace element exposures.

Bone Mineral Composition Among Long-Term Parenteral Nutrition Patients: Postmortem Assessment of Calcium, Phosphorus, Magnesium, and Select Trace Elements.

BACKGROUND: Patients receiving long-term parenteral nutrition (PN) treatment are at risk of developing metabolic bone diseases (MBDs). The bone compartment serves as a repository for a range of metal(loid)s that are administered intravenously to patients via PN solutions. Thus, the mineral composition of patient bones may be linked to the development of MBDs in this group. METHODS: We measured 12 elements in bone samples obtained post mortem from 7 long-term (2-21 years) PN patients and 18 control bones obtained from hip/knee replacement surgery. The samples were cleaned, digested, and subsequently analyzed using a method based on inductively coupled plasma tandem mass spectrometry. RESULTS: Compared with the control group, bones obtained from PN patients were significantly (P < 0.05) depleted in calcium (Ca), phosphorus (P), magnesium (Mg), chromium, and strontium and enriched in manganese (Mn), zinc, barium, cadmium (Cd), and uranium (U). No differences were observed for cobalt or lead. CONCLUSIONS: Depletion of major components of bone mineral (Ca, P, and Mg) and enrichment in known toxicants (Cd, Mn, U) are concerns for PN patients.

Dietary contributions to increased background lead, mercury, and cadmium in 9-11 Year old children: Accounting for racial differences.

BACKGROUND: Initial interest in the adverse consequences of exposure to lead (Pb), mercury (Hg), and cadmium (Cd) focused on relatively high exposures through environmental or occupational sources; however, recent evidence suggests even low-level background exposure to non-essential metals might be detrimental, particularly for children's health and development. One potentially important source of increased background levels of non-essential toxic metals is diet. OBJECTIVES: We considered whether differences in diet are associated with levels of non-essential metals in blood and whether racial differences in metals are mediated by dietary differences. METHODS: We assessed blood levels of Pb, Hg, and Cd in a sample of 9-11 year-old children (N = 295) comprised of 42% European Americans (EAs), 58% African American (AAs), and 47% female. Diet was assessed using 24-h dietary recalls during phone interviews administered to parents on two consecutive days (Friday and Saturday). The Healthy Eating Index-2105 (HEI-2015) was calculated to assess diet quality. RESULTS: The current study identified significant dietary sources of non-essential metal exposure - namely total fruit for Pb, total protein for Hg, and greens and beans for Cd. Moreover, AAs were found to have significantly higher blood levels of Pb and Hg than EAs and these racial differences were significantly mediated by these dietary differences. DISCUSSION: This study is one of very few to consider total diet in children and exposure to the non-essential metals Pb, Hg, and Cd, and the first to demonstrate that racial differences in increased background blood levels of non-essential toxic metals can be accounted for by racial differences in diet. Given regional differences in food consumption patterns and specific farm and store sources for the foods, the generalizability of the current findings has yet to be determined; however, commonly consumed foods appear to be a significant source of low-level non-essential metals.

Opportunities for evaluating chemical exposures and child health in the United States: the Environmental influences on Child Health Outcomes (ECHO) Program.

The Environmental Influences on Child Health Outcomes (ECHO) Program will evaluate environmental factors affecting children's health (perinatal, neurodevelopmental, obesity, respiratory, and positive health outcomes) by pooling cohorts composed of >50,000 children in the largest US study of its kind. Our objective was to identify opportunities for studying chemicals and child health using existing or future ECHO chemical exposure data. We described chemical-related information collected by ECHO cohorts and reviewed ECHO-relevant literature on exposure routes, sources, and environmental and human monitoring. Fifty-six ECHO cohorts have existing or planned chemical biomonitoring data for mothers or children. Environmental phenols/parabens, phthalates, metals/metalloids, and tobacco biomarkers are each being measured by ≥15 cohorts, predominantly during pregnancy and childhood, indicating ample opportunities to study child health outcomes. Cohorts are collecting questionnaire data on multiple exposure sources and conducting environmental monitoring including air, dust, and water sample collection that could be used for exposure assessment studies. To supplement existing chemical data, we recommend biomonitoring of emerging chemicals, nontargeted analysis to identify novel chemicals, and expanded measurement of chemicals in alternative biological matrices and dust samples. ECHO's rich data and samples represent an unprecedented opportunity to accelerate environmental chemical research to improve the health of US children.

Coal smoke, gestational cadmium exposure, and fetal growth.

BACKGROUND: Gestational cadmium exposure may impair fetal growth. Coal smoke has largely been unexplored as a source of cadmium exposure. We investigated the relationship between gestational cadmium exposure and fetal growth, and assessed coal smoke as a potential source of airborne cadmium, among non-smoking pregnant women in Ulaanbaatar, Mongolia, where coal combustion in home heating stoves is a major source of outdoor and indoor air pollution. METHODS: This observational study was nested within the Ulaanbaatar Gestation and Air Pollution Research (UGAAR) study, a randomized controlled trial of portable high efficiency particulate air (HEPA) filter air cleaner use during pregnancy, fetal growth, and early childhood development. We measured third trimester blood cadmium concentrations in 374 out of 465 participants who had a live birth. We used multiple linear and logistic regression to assess the relationships between log2-transformed maternal blood cadmium concentrations and birth weight, length, head circumference, ponderal index, low birth weight, small for gestational age, and preterm birth in crude and adjusted models. We also evaluated the relationships between log2-transformed blood cadmium concentrations and the density of coal-burning stoves within 5000 m of each participant's apartment as a proxy of coal smoke emissions from home heating stoves. RESULTS: The median (25th,75th percentile) blood cadmium concentration was 0.20 (0.15, 0.29) µg/L. A doubling of blood cadmium was associated with a 95 g (95% CI: 34, 155 g) reduction in birth weight in adjusted models. An interquartile range increase in coal stove density (from 3.4 to 4.9 gers/hectare) surrounding participants' apartments was associated with a 12.2% (95% CI: 0.3, 25.6%) increase in blood cadmium concentrations. CONCLUSIONS: Gestational cadmium exposure was associated with reduced birth weight. In settings where coal is a widely used fuel, cadmium may play a role in the putative association between air pollution and impaired fetal growth.

A study of lead uptake and distribution in horns from lead-dosed goats using synchrotron radiation-induced micro X-ray fluorescence elemental imaging.

OBJECTIVE: The principal goal of this study was to investigate the uptake and distribution of lead (Pb) in the horns of Pb-dosed goats, and to explore possible links to their historical Pb dosing records. Horn is a keratinized material that grows in discrete increments with the potential to preserve the historical record of past environmental exposures. While previous studies have leveraged this potential to examine environmental and biological phenomena in horns, Pb uptake has never been explored. METHODS: Horns were collected post-mortem from three goats that had been previously used to produce blood lead reference materials for the New York State proficiency testing program. The animals were periodically dosed with lead acetate, administered orally in a capsule, over a 5 to 8-year period. Horn cross sections were taken from each animal and analyzed using synchrotron radiation-induced micro X-ray fluorescence spectrometry (SR-µXRF) at the Cornell High Energy Synchrotron Source (CHESS). RESULTS: Elemental distribution maps were obtained by SR-µXRF for Pb, Ca, S, Se, and three other elements (Br, Zn and Cu), with values reported quantitatively as a mass fraction (µg/g for trace elements and mg/g for Ca and S). Accumulations of Pb were clearly visible as a series of narrow "rings" in each of the horn samples analyzed. The elements Ca, S, Br, Zn, and Cu were also detected as discrete rings within each cross-section, with Br strongly correlated with S in the samples examined. A marginal increase in Se may coincide with Pb accumulation in horn cross-sections. Annual mineralization estimates based on the relative distribution of Ca and S were used to establish a tentative timeline for horn growth, with each timeline linked to the pattern of Pb accumulation in the corresponding horn cross-section sample. CONCLUSIONS: Following ingestion, absorbed Pb is eventually deposited into caprine horns, resulting in discrete accumulations or "rings." Elemental mapping by SR-µXRF clearly show Ca-rich layers that vary with annual periodicity, consistent with previous reports of horn mineralization. Localized enrichment of Cu, Zn, Br and S appear to coincide with the keratinized regions related to the annual growth ring pattern in horns. Spatial analysis of horns for Pb accumulation may be useful as a qualitative marker of time-resolved exposures that may reflect specific periods of acute Pb absorption.

The effect of portable HEPA filter air cleaners on indoor PM2.5 concentrations and second hand tobacco smoke exposure among pregnant women in Ulaanbaatar, Mongolia: The UGAAR randomized controlled trial.

BACKGROUND: Portable HEPA filter air cleaners can reduce indoor fine particulate matter (PM2.5), but their use has not been adequately evaluated in high pollution settings. We assessed air cleaner effectiveness in reducing indoor residential PM2.5 and second hand smoke (SHS) exposures among non-smoking pregnant women in Ulaanbaatar, Mongolia. METHODS: We randomized 540 participants to an intervention group receiving 1 or 2 HEPA filter air cleaners or a control group receiving no air cleaners. We followed 259 intervention and 253 control participants to the end of pregnancy. We measured one-week indoor residential PM2.5 concentrations in early (~11weeks gestation) and late (~31weeks gestation) pregnancy and collected outdoor PM2.5 data from centrally-located government monitors. We assessed blood cadmium in late pregnancy. Hair nicotine was quantified in a subset (n=125) to evaluate blood cadmium as a biomarker of SHS exposure. We evaluated air cleaner effectiveness using mixed effects and multiple linear regression models and used stratified models and interaction terms to evaluate potential modifiers of effectiveness. RESULTS: The overall geometric mean (GM) one-week outdoor PM2.5 concentration was 47.9µg/m3 (95% CI: 44.6, 51.6µg/m3), with highest concentrations in winter (118.0µg/m3; 110.4, 126.2µg/m3). One-week indoor and outdoor PM2.5 concentrations were correlated (r=0.69). Indoor PM2.5 concentrations were 29% (21, 37%) lower in intervention versus control apartments, with GMs of 17.3µg/m3 (15.8, 18.8µg/m3) and 24.5µg/m3 (22.2, 27.0µg/m3), respectively. Air cleaner effectiveness was greater when air cleaners were first deployed (40%; 31, 48%) than after approximately five months of use (15%; 0, 27%). Blood cadmium concentrations were 14% (4, 23%) lower among intervention participants, likely due to reduced SHS exposure. CONCLUSIONS: Portable HEPA filter air cleaners can lower indoor PM2.5 concentrations and SHS exposures in highly polluted settings.

Declines in adult blood lead levels in New York City compared with the United States, 2004-2014.

OBJECTIVES: To assess changes in lead exposure in the New York City (NYC) adult population over a 10-year period and to contrast changes with national estimates, overall, and by socio-demographics and smoking status. METHODS: We used measurements of blood lead levels (BLLs) from NYC resident adults who participated in the NYC Health and Nutrition Examination Surveys (HANES) in 2004 and 2013-2014. We compared estimates of geometric means (GM), 95th percentiles, and prevalence of BLL ≥ 5 µg/dL overall and by subgroups over time, with adults who participated in the National HANES (NHANES) 2001-2004 and 2011-2014. RESULTS: The GM BLLs among NYC adults declined from 1.79 µg/dL in 2004 to 1.13 µg/dL in 2013-2014 (P < .0001). The declines over this period ranged from 30.1% to 43.2% across socio-demographic groups and smoking status (P < .0001 for all comparisons), and were slightly greater than declines observed nationally. The drop in prevalence of elevated BLLs (≥ 5 µg/dL) was also greater in NYC (4.8-0.5%), compared with NHANES (3.8-2.0%). By 2013-2014, NYC adults with lower annual family income (< $20,000) no longer had higher GM BLLs relative to those with higher incomes (≥ $75,000), a disparity improvement not observed nationally. Likewise, GM BLLs and 95th percentiles for non-Hispanic black adults in NYC were lower than GM BLLs for non-Hispanic white adults. Non-Hispanic Asian adults had the highest GM BLLs compared with other racial/ethnic groups, both in NYC in 2013-14 and nationally in 2011-2014 (1.37 µg/dL, P = .1048 and 1.22 µg/dL, P = .0004, respectively). CONCLUSION: The lessening of disparity in lead exposure across income groups and decreasing exposure at the high end of the distribution among non-Hispanic black and Asian adults in NYC suggest that regulatory and outreach efforts have effectively targeted these higher exposure risk groups. However, Asian adults still had the highest average BLL, suggesting a need for enhanced outreach to this group. Local surveillance remains an important tool to monitor BLLs of local populations and to inform initiatives to reduce exposures in those at highest risk.

Associations between IVF outcomes and essential trace elements measured in follicular fluid and urine: a pilot study.

PURPOSE: A hypothesis-generating pilot study exploring associations between essential trace elements measured in follicular fluid (FF) and urine and in vitro fertilization (IVF) endpoints. METHODS: We recruited 58 women undergoing IVF between 2007 and 2008, and measured cobalt, chromium, copper, manganese, molybdenum, and zinc in FF (n = 46) and urine (n = 45) by inductively coupled plasma mass spectrometry (ICP-MS). We used multivariable regression models to assess the impact of FF and urine trace elements on IVF outcomes, adjusted for age, body mass index, race, and cigarette smoking. RESULTS: Trace elements were mostly present at lower concentrations in FF than in urine. The average number of oocytes retrieved was positively associated with higher urine cobalt, chromium, copper, and molybdenum concentrations. FF chromium and manganese were negatively associated with the proportion of mature oocytes, yet urine manganese had a positive association. FF zinc was inversely associated with average oocyte fertilization. Urine trace elements were significant positive predictors for the total number of embryos generated. FF copper predicted lower embryo fragmentation while urine copper was associated with higher embryo cell number and urine manganese with higher embryo fragmentation. No associations were detected for implantation, pregnancy, or live birth. CONCLUSIONS: Our results suggest the importance of trace elements in both FF and urine for intermediate, although not necessarily clinical, IVF endpoints. The results differed using FF or urine biomarkers of exposure, which may have implications for the design of clinical and epidemiologic investigations. These initial findings will form the basis of a more definitive future study.

Abundance and Significance of Iron, Zinc, Copper, and Calcium in the Hearts of Patients With Friedreich Ataxia.

Cardiomyopathy is a frequent cause of death in patients with Friedreich ataxia (FA), and a characteristic pathological feature is the focal accumulation of iron (Fe) in cardiomyocytes. This restricted localization of the metal contrasts with the diffuse cardiac Fe overload in hemochromatosis and transfusion siderosis. Nevertheless, heart Fe in FA contributes to cardiomyocyte necrosis, inflammation, and scarring as the disease progresses. A putative mechanism of cardiomyopathy in FA is Fe-mediated oxidative damage. Two other transition metals zinc (Zn) and copper (Cu), are diffusely distributed throughout normal hearts and the hearts of patients with FA. The myocardium in FA is also prone to deposits of calcium in the form of scattered concretions. In this study, heart tissues (left and right ventricular walls and ventricular septum) of 23 patients with genetically confirmed FA and 8 normal controls were obtained at autopsy and analyzed for Fe, Zn, Cu, and calcium. The principal assay methods were inductively coupled plasma optical emission spectrometry and plasma mass spectrometry. Total levels of Fe in bulk extracts were not significantly higher than normal, and the concentrations of Zn also remained in the normal range. Cu levels, however, were significantly lower in FA. In conclusion, the decrease of Cu may be important in consideration of the potential benefit of Cu supplements in FA cardiomyopathy.

Secondhand Tobacco Smoke Exposure and Neuromotor Function in Rural Children.

OBJECTIVE: To investigate the relationship between secondhand tobacco smoke (SHS) exposure and neuromotor function in children. STUDY DESIGN: We studied 404 children aged 7-9 years who were exposed to SHS and other environmental neurotoxicants. Parents reported smoking habits, and serum cotinine levels were measured in children to determine SHS exposure. The Halstead-Reitan Finger Oscillation Test, Purdue Grooved Pegboard Test-Kiddie version, and Bruininks-Oseretsky Test of Motor Proficiency 2-Short Form were used to assess neuromotor function. Multivariable regression models that accounted for potential confounders were used to evaluate the associations. RESULTS: Approximately 50% of the children were exposed to SHS based on serum cotinine measures. Exposure to SHS was significantly associated with motor impairment in children, including diminished visuomotor coordination (P = .01), fine motor integration (P = .01), balance (P = .02), and strength (P = .04) after adjusting for exposures to lead and manganese, age, sex, body mass index, measures of parental cognitive abilities, parental education, and quality of home environment. CONCLUSION: SHS is a neurotoxicant that may be associated with impaired childhood neuromotor function.

Low-level mercury in children: associations with sleep duration and cytokines TNF-α and IL-6.

There is a sizeable literature suggesting that mercury (Hg) exposure affects cytokine levels in humans. In addition to their signaling role in the immune system, some cytokines are also integrally associated with sleep behavior. In this cross-sectional study of 9-11 year old children (N=100), we measured total blood Hg in whole blood, serum levels of tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6), and objectively measured sleep and activity using actigraphy. Increasing blood Hg was associated with significantly shorter sleep duration and lower levels of TNF-α. IL-6 was not associated with sleep or blood Hg. This study is the first to document an association between total blood Hg and sleep (albeit a small effect), and the first to consider the associations of total blood Hg with cytokines TNF-α and IL-6 in a pediatric sample. Further research using alternative designs (e.g., time-series) is necessary to determine if there is a causal pathway linking low-level Hg exposure to sleep restriction and reduced cytokines.