Phthalate and phthalate replacement concentrations in relationship to adiposity in a multi-racial cohort of children.

BACKGROUND/OBJECTIVE: Phthalates and phthalate replacements are used in multiple everyday products, making many of them bioavailable to children. Experimental studies suggest that phthalates and their replacements may be obesogenic, however, epidemiologic studies remain inconsistent. Therefore, our objective was to examine the association between phthalates, phthalate replacements and childhood adiposity/obesity markers in children. SUBJECTS/METHODS: A cross-sectional study was conducted in 630 racial/ethnically diverse children ages 4-8 years. Urinary oxidative metabolites of DINCH and DEHTP, three low molecular weight (LMW) phthalates, and eleven high molecular weight (HMW) phthalates were measured. Weight, height, waist circumference and % body fat were measured. Composite molar sum groups (nmol/ml) were natural log-transformed. Linear regression models adjusted for urine specific gravity, sex, age, race-ethnicity, birthweight, breastfeeding, reported activity level, mother's education and pre-pregnancy BMI. RESULTS: All children had LMW and HMW phthalate metabolites and 88% had DINCH levels above the limit of detection. One unit higher in the log of DINCH was associated with 0.106 units lower BMI z-score [ß = -0.106 (95% CI: -0.181, -0.031)], 0.119 units lower waist circumference z-score [ß = -0.119 (95% CI: -0.189, -0.050)], and 0.012 units lower percent body fat [ß = -0.012 (95% CI: -0.019, -0.005)]. LMW and HMW group values were not associated with adiposity/obesity. CONCLUSIONS: We report an inverse association between child urinary DINCH levels, a non-phthalate plasticizer that has replaced DEHP in several applications, and BMI z-score, waist circumference z-score and % body fat in children. Few prior studies of phthalates and their replacements in children have been conducted in diverse populations. Moreover, DINCH has not received a great deal of attention or regulation, but it is a common exposure. In summary, understanding the ubiquitous nature of these chemical exposures and ultimately their sources will contribute to our understanding of their relationship with obesity.

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.

Arsenic Methyltransferase and Apolipoprotein E Polymorphism in Pregnant Women Exposed to Inorganic Arsenic in Drinking Water in Western Romania.

Previous studies have shown that inorganic arsenic (iAs) exposure may be associated with genotoxic and cytotoxic effects. The aim of this study was to evaluate the relationship between several polymorphisms in AS3MT and APOE genes and urinary As and the relationship between these polymorphisms and pregnancy loss. We determined urinary As concentrations and performed genotyping analysis in 50 cases of spontaneous pregnancy loss and 50 controls, matched to cases on gestational age. The most frequently identified AS3MT polymorphisms in both cases and controls were in rs10748835 (80% cases and 68% controls), rs3740400 (78% cases and 64% controls), rs7085104 (74% cases and 48% controls), and rs1046778 (62% cases and 54% controls). We identified 30 different haplotypes in AS3MT SNPs, with four predominant haplotypes (>8%). Cases with Haplotype 1 had four-fold higher urinary DMA and two-fold higher MMA concentration than those without this haplotype, the MMA levels were lower in cases and controls with Haplotype 4 compared to Haplotype 1, and the DMA levels were significantly lower in cases with Haplotype 4 compared to Haplotype 3. Cases with Haplotype 1 had higher levels of all analyzed biomarkers, suggesting that Haplotype 1 may be associated with greater exposure to iAs and tobacco smoke. Our results suggest the importance of the AS3MT gene in iAs metabolism among pregnant women with low-level drinking water iAs exposure.

Racial disparities affect the association between gestational urinary phthalate mixtures and infant genital measures.

Background: Phthalates are ubiquitous anti-androgenic endocrine disrupting chemicals found in personal care products, medications, and many plastics. Studies have shown a racial disparity in phthalates exposure among U.S. women, which may also impact fetal development. Methods: We conducted a prospective cohort study of gestational exposure to a phthalates mixture in a racially-diverse population to determine their association with genital development. Mid-gestation (18-22 weeks) urine was collected from 152 women who self-identified as non-Hispanic Black and 158 women who self-identified as non-Hispanic White in Charleston, South Carolina between 2011 and 2014. We measured eight phthalate monoester metabolites in urine using liquid chromatography tandem-mass spectrometry. Mid-gestational penile dimensions were measured using ultrasound and anogenital distances were measured postnatally. We used Bayesian kernel machine regression to estimate the associations among the mixture of phthalate metabolites and mid-gestation penile dimensions and postnatal anogenital distance measures among singleton male (n = 179) and female (n = 131) infants, adjusted for urinary specific gravity, maternal age, body mass index, education level, cigarette smoking, and gestational age at enrollment or birth weight z-score. Results: We found a stronger association between greater phthalates and decreased anopenile distance among infants born to women who self-identified as Black. Mono (2-ethylhexyl) phthalate (MEHP) was the driving mixture component among Black women, and monobutyl phthalate (MBP) and monoethyl phthalate (MEP) were drivers among White women. We also identified a non-linear association between phthalates and lesser ultrasound penile volume among women who self-identified as Black with monoisobutyl phthalate (MiBP) and MBP being most important. We also found an association between greater phthalates and shorter anoclitoral distance among infants born to women who self-identified as Black, with MEP and monobenzyl phthalate (MBzP) contributing most to this association. Conclusion: Our results suggest a disparity in the association between gestational exposure to a mixture of phthalates and fetal genital development among women who self-identified as Black compared to White.

Prenatal Exposure to PFAS, Associations with Preterm Birth and Modification by Maternal Estrogen Levels: The Maoming Birth Study.

BACKGROUND: Estrogens play a critical role in parturition, and poly- and perfluoroalkyl substances (PFAS), which have estrogenic effects, have been associated with preterm birth. However, the impact of estrogens on the association between PFAS and preterm birth is unknown. OBJECTIVE: The objective of this study is to investigate if estrogens modified the association between PFAS and preterm birth, using a nested case-control study design. METHODS: A total of 371 preterm births and 508 controls were selected from a birth cohort study in China between 2016 and 2018. Perfluorobutanoic acid (PFBA), perfluorohexanesulfonic acid (PFHxS) and its branched isomer, perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS) and its branched isomer, and perfluorononanoic acid (PFNA) were quantified in maternal serum (mean gestational age of 32 wk). Estradiol and estriol were quantified in cord serum. Preterm birth was defined as live delivery at <37 gestational weeks. Causal mediation analysis was used to estimate the mediation and interaction effects of estrogen on the association between PFAS and preterm birth. Latent profile analysis was used to identify important estrogen profiles. Multiple linear regression was used to estimate associations between PFAS and preterm birth and interactions between PFAS and estrogens on preterm birth. RESULTS: Overall, higher odds ratios (ORs) of preterm birth were associated with each 1 ln-unit PFAS increase: PFBA [1.20, 95% confidence interval (CI): 1.14, 1.26], PFNA (1.30, 95% CI: 1.21, 1.39), PFOA (1.98, 95% CI: 1.54, 2.55), and PFOS (1.91, 95% CI: 1.76, 2.07) and its branched isomer (1.91, 95% CI: 1.90, 1.92). We detected statistically significant interactions between cord estradiol and PFAS on preterm birth, while no mediation effects of cord estrogen were observed. The ORs of PFOS (4.29, 95% CI: 1.31, 8.25), its branched isomer (6.71, 95% CI: 1.06, 11.91), and preterm birth were greater for participants with high cord estrogen levels than for participants with low cord estrogen levels. DISCUSSION: Our findings suggest that estrogen modified the association between maternal PFAS exposure and preterm birth. Further studies on maternal PFAS exposure and preterm birth, taking interaction effects of cord estrogens into account, are warranted. https://doi.org/10.1289/EHP11377.

Urinary arsenic and spontaneous pregnancy loss - a hypothesis-generating case-control investigation in western Romania.

Arsenic occurs as a natural contaminant of drinking water supplies in arsenic endemic areas, posing a threat to public health. Our aim was to evaluate the relationship between urinary arsenic concentrations and spontaneous pregnancy loss in a population with low-moderate level drinking water arsenic exposure (mostly <10 µg/L). We enrolled 150 women with incident spontaneous pregnancy losses and 150 controls with ongoing pregnancies matched by gestational age. We measured arsenic species in urine using high performance liquid chromatography paired to inductively coupled plasma mass spectrometry. Urinary arsenic was not related to spontaneous pregnancy loss in conditional logistic regression models adjusted for confounding factors. However, a 10 µg/L increase in urinary arsenic (III + V) salt concentrations was associated with 8.00-fold (95% CI: 0.68, 3.35 × 105) greater odds of spontaneous loss among women using prenatal vitamins in an interaction model (P for interaction = 0.07), although the effect estimate was imprecise. In an additional interaction model, prenatal vitamin use was associated with lower odds of loss (OR = 0.30; 95% CI: 0.13, 0.66), although the association was diminished in the presence of a 10 µg/L increase in urinary inorganic arsenic (OR = 0.44; 95% CI: 0.70, 3.22). Total urinary arsenic was associated with 1.48-fold (95% CI: 0.20, 11.35) greater odds for loss among women with urinary cotinine >50 µg/L in another interaction model (P for interaction = 0.07). These results suggest a potential modest increase in the odds of pregnancy loss associated with increased total urinary arsenic among women smoking during pregnancy (urinary cotinine >50 µg/L). Prenatal vitamin use may act as a protective factor for arsenic exposure associated pregnancy loss, but appears to be less protective with increasing urinary inorganic arsenic concentrations.

A systematic evidence map for the evaluation of noncancer health effects and exposures to polychlorinated biphenyl mixtures.

Assessing health outcomes associated with exposure to polychlorinated biphenyls (PCBs) is important given their persistent and ubiquitous nature. PCBs are classified as a Group 1 carcinogen, but the full range of potential noncancer health effects from exposure to PCBs has not been systematically summarized and evaluated. We used systematic review methods to identify and screen the literature using combined manual review and machine learning approaches. A protocol was developed that describes the literature search strategy and Populations, Exposures, Comparators, and Outcomes (PECO) criteria used to facilitate subsequent screening and categorization of literature into a systematic evidence map of PCB exposure and noncancer health endpoints across 15 organs/systems. A comprehensive literature search yielded 62,599 records. After electronic prioritization steps, 17,037 studies were manually screened at the title and abstract level. An additional 900 studies identified by experts or supplemental searches were also included. After full-text screening of 3889 references, 1586 studies met the PECO criteria. Relevant study details such as the endpoints assessed, exposure duration, and species were extracted into literature summary tables. This review compiles and organizes the human and mammalian studies from these tables into an evidence map for noncancer health endpoints and PCB mixture exposure to identify areas of robust research as well as areas of uncertainty that would benefit from future investigation. Summary data are available online as interactive visuals with downloadable metadata. Sufficient research is available to inform PCB hazard assessments for most organs/systems, but the amount of data to inform associations with specific endpoints differs. Furthermore, despite many years of research, sparse data exist for inhalation and dermal exposures, which are highly relevant human exposure routes. This evidence map provides a foundation for future systematic reviews and noncancer hazard assessments of PCB mixtures and for strategic planning of research to inform areas of greater uncertainty.

Association between gestational PFAS exposure and Children's adiposity in a diverse population.

Perfluoroalkyl substances (PFAS) are widely distributed suspected obesogens that cross the placenta. However, few data are available to assess potential fetal effects of PFAS exposure on children's adiposity in diverse populations. To address the data gap, we estimated associations between gestational PFAS concentrations and childhood adiposity in a diverse mother-child cohort. We considered 6 PFAS in first trimester blood plasma, measured using ultra-high-performance liquid chromatography with tandem mass spectrometry, collected from non-smoking women with low-risk singleton pregnancies (n = 803). Body mass index (BMI), waist circumference (WC), fat mass, fat-free mass, and % body fat were ascertained in 4-8 year old children as measures of adiposity. We estimated associations of individual gestational PFAS with children's adiposity and overweight/obesity, adjusted for confounders. There were more non-Hispanic Black (31.7 %) and Hispanic (42.6 %) children with overweight/obesity, than non-Hispanic white (18.2 %) and Asian/Pacific Islander (16.4 %) children (p < 0.0001). Perfluorooctane sulfonate (PFOS; 5.3 ng/mL) and perfluorooctanoic acid (2.0 ng/mL) had the highest median concentrations in maternal blood. Among women without obesity (n = 667), greater perfluoroundecanoic acid (PFUnDA) was associated with their children having higher WC z-score (ß = 0.08, 95%CI: 0.01, 0.14; p = 0.02), fat mass (ß = 0.55 kg, 95%CI: 0.21, 0.90; p = 0.002), and % body fat (ß = 0.01 %; 95%CI: 0.003, 0.01; p = 0.004), although the association of PFUnDA with fat mass attenuated at the highest concentrations. Among women without obesity, the associations of PFAS and their children's adiposity varied significantly by self-reported race-ethnicity, although the direction of the associations was inconsistent. In contrast, among the children of women with obesity, greater, PFOS, perfluorononanoic acid, and perfluorodecanoic acid concentrations were associated with less adiposity (n = 136). Our results suggest that specific PFAS may be developmental obesogens, and that maternal race-ethnicity may be an important modifier of the associations among women without obesity.

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.

Reproductive Health Risks Associated with Occupational and Environmental Exposure to Pesticides.

A marked reduction in fertility and an increase in adverse reproductive outcomes during the last few decades have been associated with occupational and environmental chemical exposures. Exposure to different types of pesticides may increase the risks of chronic diseases, such as diabetes, cancer, and neurodegenerative disease, but also of reduced fertility and birth defects. Both occupational and environmental exposures to pesticides are important, as many are endocrine disruptors, which means that even very low-dose exposure levels may have measurable biological effects. The aim of this review was to summarize the knowledge collected between 2000 and 2020, to highlight new findings, and to further interpret the mechanisms that may associate pesticides with infertility, abnormal sexual maturation, and pregnancy complications associated with occupational, environmental and transplacental exposures. A summary of current pesticide production and usage legislation is also included in order to elucidate the potential impact on exposure profile differences between countries, which may inform prevention measures. Recommendations for the medical surveillance of occupationally exposed populations, which should be facilitated by the biomonitoring of reduced fertility, is also discussed.

Association between gestational phthalate exposure and newborn head circumference; impacts by race and sex.

Observational and experimental studies report associations between gestational phthalate exposure and fetal development, yet few data exist to characterize phthalate effects on head circumference (HC) or to estimate the impact of race or sex. To address this data gap, we enrolled 152 African American and 158 white mothers with uncomplicated singleton pregnancies from the Charleston, South Carolina (USA) metropolitan area in a prospective birth cohort. Study participants provided up to two urine specimens during mid and late gestation, completed a study questionnaire, and allowed access to hospital birth records. We measured eight phthalate monoester metabolites using liquid chromatography with tandem mass spectrometry, and calculated molar sums of phthalate parent diesters. After specific gravity correction, we tested for associations between phthalates and neonatal HC (cm) and cephalization index (cm/g) using multiple informant linear regression with inverse probability weighting to account for selection bias between repeated urine sampling, adjusted for maternal race, age, body mass index, education, and smoking. We explored interactions by maternal race and infant sex. A doubling of urinary monoethyl phthalate (MEP) concentration was associated with a -0.49% (95%CI: -0.95%, -0.02%) smaller head circumference, although seven other phthalate metabolites were null. There were no statistically significant associations with cephalization index. HC was larger for whites than African American newborns (p < 0.0001) but similar for males and females (p = 0.16). We detected interactions for maternal race with urinary monobutyl phthalate (MBP; p = 0.03), monobenzyl phthalate (MBzP; p = 0.01), monoethylhexyl phthalate (MEHP; p = 0.05), monomethyl phthalate (MMP; p = 0.02), and the sum of dibutyl phthalate metabolites (∑DBP; p = 0.05), in which reduced HC circumference associations were stronger among whites than African Americans, and interactions for sex with MBP (p = 0.08) and MiBP (p = 0.03), in which associations were stronger for females than males. Our results suggest that gestational phthalate exposure is associated with smaller neonatal HC and that white mothers and female newborns have greater susceptibility.

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.

The role of influenza vaccination in mitigating the adverse impact of ambient air pollution on lung function in children: New insights from the Seven Northeastern Cities Study in China.

BACKGROUND: Ambient air pollution exposure and influenza virus infection have been documented to be independently associated with reduced lung function previously. Influenza vaccination plays an important role in protecting against influenza-induced severe diseases. However, no study to date has focused on whether influenza vaccination may modify the associations between ambient air pollution exposure and lung function. METHODS: We undertook a cross-sectional study of 6740 children aged 7-14 years into Seven Northeast Cities (SNEC) Study in China during 2012-2013. We collected information from parents/guardians about sociodemographic factors and influenza vaccination status in the past three years. Lung function was measured using portable electronic spirometers. Machine learning methods were used to predict 4-year average ambient air pollutant exposures to nitrogen dioxide (NO2) and particulate matter with an aerodynamic diameter <1 µm (PM1), <2.5 µm (PM2.5) and <10 µm (PM10). Two-level linear and logistic regression models were used to assess interactions between influenza vaccination and long-term ambient air pollutants exposure on lung function reduction, controlling for potential confounding factors. RESULTS: Ambient air pollution were observed significantly associated with reductions in lung function among children. We found significant interactions between influenza vaccination and air pollutants on lung function, suggesting greater vulnerability to air pollution among unvaccinated children. For example, an interaction (pinteraction = 0.002) indicated a -283.44 mL (95% CI: -327.04, -239.83) reduction in forced vital capacity (FVC) per interquartile range (IQR) increase in PM1 concentrations among unvaccinated children, compared with the -108.24 mL (95%CI: -174.88, -41.60) reduction in FVC observed among vaccinated children. Results from logistic regression models also showed stronger associations between per IQR increase in PM1 and lung function reduction measured by FVC and peak expiratory flow (PEF) among unvaccinated children than the according ORs among vaccinated children [i.e., Odds Ratio (OR) for PM1 and impaired FVC: 2.33 (95%CI: 1.79, 3.03) vs 1.65 (95%CI: 1.20, 2.28); OR for PM2.5 and impaired PEF: 1.45 (95%CI: 1.12,1.87) vs 1.04 (95%CI: 0.76,1.43)]. The heterogeneity of the modification by influenza vaccination of the associations between air pollution exposure and lung function reduction appeared to be more substantial in girls than in boys. CONCLUSION: Our results suggest that influenza vaccination may moderate the detrimental effects of ambient air pollution on lung function among children. This study provides new insights into the possible co-benefits of strengthening and promoting global influenza vaccination programs among children.

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.

The time window of pet ownership exposure modifies the relationship of Environmental Tobacco Smoke with lung function: A large population-based cohort study.

There is a large body of evidence linking Environmental Tobacco Smoke (ETS) exposure with impaired lung function. However, it is not known whether exposure to pets modifies this relationship. To investigate if pet ownership changes the association between ETS exposure and lung function, a population-based sample of 7326 children, 7-14 years old, were randomly recruited from 24 districts in northeast China. Lung function including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), peak expiratory flow (PEF), and maximal mid-expiratory flow (MMEF) was measured by spirometry, while pet ownership time periods and ETS exposure were collected by questionnaire. Two-level regression analysis was done, with covariates controlled for. The results showed pet exposure in certain early lifetime windows modified the associations of ETS exposure on decreased lung function in children. Among children exposed to current ETS, those exposed to pets in utero had greater reductions in lung function (for instance: OR for reduced FVC (<85% predicted) = 10.86; 95% CI: 3.80-30.97) than those not exposed to pets in utero (OR = 2.32; 95% CI: 1.76-3.05) (pinteraction = 0.005). While, children exposed to current pet ownership reduced the lung function impairment induced by ETS exposure during the first 2 years of life and/or ETS exposure during pregnancy, especially for FVC impairment. For instance, OR (95%CI) for reduced FVC (<85% predicted) was 0.81 (0.56, 1.18) and 1.42 (1.15, 1.74), respectively, for children with or without current pet ownership exposed to ETS during the first 2 years of life (pinteraction = 0.010). Furthermore, pet type or number of pets did not significantly modify associations between ETS exposure and lung function. In conclusion, the timing of pet ownership modified associations between ETS exposure and lung function, pet ownership in utero and during the first 2 years of life significantly worsened the adverse impacts of passive smoking on lung function.

Pet ownership in utero and in childhood decreases the effects of environmental tobacco smoke exposure on hypertension in children: A large population based cohort study.

BACKGROUND: Little is known about whether exposure to pets influences the association between hypertension and environmental tobacco smoke (ETS). The current study aims to examine the interaction of pet ownership on ETS exposure and the development of hypertension in children. METHODS: From 2012 to 2013, a total of 9354 children, 5 to 17 years of age, were recruited from 62 schools in seven northeastern cities. BP in children was measured and hypertension was defined as an average diastolic blood pressure (DBP) or systolic blood pressure (SBP) at or above the 95th percentile for that child's age, sex, and height. Pet ownership in three different time periods (in utero, past 2 years, and currently) and ETS exposure data were collected from parents via a questionnaire. Two-level regressions were used for the data analyses. RESULTS: The data show consistent, significant interactions between exposure to pets and effects from ETS. Children who were not exposed to pets experienced stronger effects from ETS on hypertension when compared to those exposed to pets, and the protective effect of pet ownership became stronger with a greater number of pets in the home. Exposure to in utero ETS was associated with hypertension [adjusted odds ratio (aOR) = 1.32, 95% confidence interval (CI): 1.13-1.54] only for those children without pet exposure in utero but not for those with pets (aOR = 0.75; 95% CI: 0.49-1.15) (pinteraction < 0.05). Moreover, household dog ownership was related to significantly lower effects of current ETS on hypertension (aOR = 0.80, 95% CI: 0.61-1.05) compared with children without dogs (aOR = 1.26, 95% CI: 1.11-1.44) (pinteraction = 0.001). Interaction associations between ETS and pet ownership were more robust for girls than for boys and for younger than older children. CONCLUSION: This study indicates an inverse relationship between pet ownership and ETS, potentially pointing to pet ownership as protecting against the development of hypertension in children.

A longitudinal study of polychlorinated biphenyls and neuropsychological function among older adults from New York State.

BACKGROUND: Cross-sectional studies have linked greater polychlorinated biphenyl (PCB) exposure to adverse neuropsychological effects in older adults, including learning, memory, and depressive symptoms. However, no studies among older adults have evaluated the association over time. OBJECTIVES: To assess the effect of serum PCB levels on neuropsychological function over a 14-year period in a cohort of older men and women from a PCB-contaminated area of New York State. METHODS: In 2000-2002, we assessed serum PCB levels and neuropsychological function (including the California Verbal Learning Test Trial 1 (CVLTT1) for verbal memory and learning, and the Beck Depression Index (BDI) for depressive symptoms) in 253 men and women, ages 55-74 years. A total of 116 (46%) persons repeated the PCB and neuropsychological assessment 14 years later. To assess the association over time, we used generalized estimating equations with clustering variables time, total PCB (∑PCB), and ∑PCB × time, and adjusted for baseline age, sex, smoking, and total serum-lipids. For statistically significant ∑PCB × time interactions, we evaluated the association between PCBs and either verbal memory and learning or depressive symptoms while holding ∑PCB constant at the 10th and 90th percentiles to clarify the direction of the interaction. RESULTS: Over the study period, serum ∑PCB levels (wet-weight) declined by 22%, and were associated with different patterns of change over time for memory (∑PCB × Time ß = 0.08 p = 0.009) and depressive symptoms (∑PCB × Time ß = -0.16 p = 0.013). Specifically, verbal memory and learning decreased (ß = -0.08 p = 0.008) and depressive symptoms increased (ß = 0.17 p = 0.008) among persons with low exposure (∑PCB levels at the 10th percentile), while persons with high exposure (90th percentile) showed non-significant improvements. DISCUSSION: In this cohort, declining ∑PCB levels were likely due at least in part to low rates of local fish consumption in recent decades, given the ban since 1976. The decreased verbal memory and learning and increased depressive symptoms over time among persons with low serum ∑PCB levels is consistent with studies of normative aging. However, the small improvements in those outcomes among those with high serum ∑PCB levels was unexpected. Healthy survivor selection bias or uncontrolled confounding may explain this result. It may also indicate that the neurotoxic impacts of PCBs in older adults are not permanent, but future studies are needed to confirm this possibility.

Trends in disability-adjusted life years of lung cancer among women from 2004 to 2030 in Guangzhou, China: A population-based study.

BACKGROUND: Forecast of disease burden in lung cancer is an important health agenda. One of the main challenges is to predict the evolution of trends in disability-adjusted life year (DALY) of lung cancer so as to anticipate the future burden and to coordinate the supply of sufficient health services and care. METHODS: Using 2004-2013 cancer registry data in Guangzhou, we fitted Bayesian age-period-cohort models with age, period, and cohort effects to analyze trends of lung cancer among women, and then made forecast for DALY of lung cancer until 2030. RESULTS: During 2004-2013, there was an annual average of 10,582 DALYs for lung cancer (15.84% of total DALY). In 2014-2030, DALY is expected to reach 234,752 person-years for lung cancer (12.25% of total DALY), with an annual mean of 13,809 DALYs. Lung cancer crude DALY rate is projected to rise steadily from 257.56 (95% uncertainty interval: 165.97-361.22) in 2014 to 316.99 (219.96-419.41) per 100,000 women in 2030, and the rise is mainly seen in 45-64 years age group. Lung cancer DALY rate remains the highest in the 65-89 years age group. CONCLUSIONS: Women at 65-89 years carry the highest lung cancer burden among other age groups in Guangzhou. The DALY rate of lung cancer is projected to increase most precipitously for the 45-64 years age group. This indicates that concerted efforts are needed to develop adequate cancer services, and to reassess health resources for control and care of lung cancer in these populations.

Preconception serum lipids and lipophilic micronutrient levels are associated with live birth rates after IVF.

RESEARCH QUESTION: Is a mixture of preconception serum lipids and lipophilic micronutrients associated with clinical pregnancy and live births? DESIGN: In this prospective cohort study, blood serum was collected on the day of oocyte retrieval for 180 women undergoing IVF at an academic reproductive health centre. Concentrations of lipids (phospholipids, total cholesterol, high- and low-density lipoproteins, and triglycerides) and lipophilic micronutrients (α-, δ-, and γ-tocopherols, retinol, ß- and α-carotenes, ß-cryptoxanthin, lutein and lycopene) were determined using diagnostic reagent kits and high-performance liquid chromatography. Poisson regression was used with robust variance estimation to evaluate changes in Z-scores for the mixture of serum lipid and lipophilic micronutrient concentrations as predictors of embryo implantation, clinical pregnancy and live birth, adjusted for age, body mass index (BMI), race, smoking status, infertility diagnosis, ovarian stimulation protocol and other measured lipid and lipophilic micronutrient concentrations. RESULTS: Each SD higher serum triglyceride concentration was associated with a lower chance of live birth (RR 0.54; 95% CI 0.33 to 0.90) whereas a 1 SD higher serum α-tocopherol concentration, as part of a mixture of serum lipids and lipophilic micronutrients, was associated with a higher likelihood for a live birth (RR 1.61; 95% CI 1.11 to 2.36). Serum ß-carotene concentrations were associated with live birth in a non-linear fashion; low ß-carotene was associated with a lower chance of live birth and high ß-carotene with a higher chance of live birth. CONCLUSION: Although components of a mixture of lipids and lipophilic micronutrients were associated with live birth outcomes after IVF, a larger investigation is necessary to fully evaluate the potential clinical implications.

Ultrafine CB-induced small airway obstruction in CB-exposed workers and mice.

The potential threat of superfine carbon black (CB) particles to human health has received attention, but there are few human toxicological data available. The purpose of this study was to investigate the relationships between serum CC16 and SP-A with small airway related pulmonary functions in CB workers. Ninety-nine male CB packers and 115 non-CB-exposed healthy male workers were recruited. Serum CC16 and/or SP-A and pulmonary function tests were evaluated, and the relationship between them were also analyzed. To further assess pulmonary damage induced by CB particles in target organs, an animal inhalation exposure study was conducted. Male C57BL/6 mice were exposed to 15 and 30 mg/m3 CB for 6 h per day for 28 days. Levels of CC16 and SP-A were evaluated by ELISA and immunohistochemical staining (IHC). The results showed a 20% decreased in median CC16 and a 15% increase in median SP-A among CB-exposed workers. FEV1%, FEV/FVC, MMEF%, FEF25%, and FEF75% were also decreased in CB-exposed workers (P < 0.05). A significant positive correlation was observed between serum CC16 concentration and FEV1/FVC, although a negative correlation was found between serum SP-A concentration and FEV1/FVC. Serum CC16 was significantly reduced by 72% in mice with high CB-exposure, and serum SPA was 1.65x and 1.17x higher than CB-unexposed control mice in low and high CB-exposed mice, respectively. Lung CC16 and serum CC16 levels were positively correlated in mice (P = 0.024). Long-term exposure to ultrafine CB particles is associated with a decrease in CC16 and an increase in SP-A in the peripheral blood of CB-exposed workers. In conclusion, superfine CB particles have the potential to cause small airway obstruction.