Faculty Bibliography

OBJECTIVE:) and outcomes related to disease severity. METHODS:levels (predictors) from the patient's ZIP Code (not publicly available) from day of admission. Outcomes were mortality, intubation, length of stay (LOS), and total costs. We calculated weighted national estimates and performed multivariable analyses adjusting for sociodemographic and hospital factors. RESULTS:levels were associated with increased odds of intubation. CONCLUSIONS:were associated with more severe presentations of pneumonia. Future work should examine these relationships in more recent years and over a longer time period.

OBJECTIVE:Studies have documented disparities in exposure to endocrine disrupting chemicals (EDC), but no studies have investigated potential implications for racial/ethnic disparities in chronic disease and associated costs. Our objective was to examine EDC levels in the US population according to race/ethnicity and to quantify disease burden and associated costs. STUDY DESIGN AND SETTING/METHODS:EDC exposure levels in 2007-2010 were obtained from the National Health and Nutrition Examination Surveys. The associated disease burden and costs for twelve exposure-response relationships were determined for Non-Hispanic Whites, Non-Hispanic Blacks, Mexican-Americans, Other Hispanics, and Other/Multicultural. RESULTS:EDC exposure levels and associated burden of disease and costs were higher in Non-Hispanic Blacks ($56.8 billion; 16.5% of total costs) and Mexican-Americans ($50.1 billion; 14.6%) compared to their proportion of the total population (12.6% and 13.5%, respectively). Associated costs among Non-Hispanic Whites comprised 52.3% of total costs ($179.8 billion), though they comprise 66.1% of the US population. These disparities are driven by generally higher exposure to persistent pesticides and flame retardants among Non-Hispanic Blacks and Mexican-Americans. CONCLUSION/CONCLUSIONS:Our estimates suggest that racial/ethnic disparities in chronic diseases in the US may be due to chemical exposures, and are an important tool to inform policies that address such disparities.

The effects of childhood exposure to perfluoroalkyl substances (PFASs) on lung function remain mostly unknown. Previous research indicates that children living or going to school near the World Trade Center (WTC) disaster were exposed to high levels of PFASs, among other toxic chemicals. To explore the effects of PFAS exposure on lung function, we measured serum PFASs in a cohort of children from the WTC Health Registry and a matched control group. Perfluorooctanesulfonate had the highest median concentrations in both groups (WTCHR = 3.72 ng/mL, Comparison = 2.75 ng/mL), while the lowest median concentrations were seen for perfluoroundecanoic acid (WTCHR = 0.12 ng/mL, Comparison = 0.01 ng/mL). Lung function outcomes were measured by spirometry, plethysmography, and oscillometry. Asthma diagnosis and serum eosinophil count were also recorded. We examined the relationships of each PFAS with lung function parameters and eosinophil count using linear regressions. Odds ratios for asthma were obtained for each PFAS using logistic regression. The effect of total PFASs on these outcomes was also assessed. All regression models were adjusted for sex, race/ethnicity, age, body mass index (BMI) and tobacco smoke exposure. We found that serum PFASs were not statistically associated with the measured lung function parameters, asthma diagnosis, or eosinophil count in this cohort (p < 0.05). These findings highlight the need for more longitudinal studies to explore the long-term effects of childhood PFAS exposure on lung function past adolescence and early adulthood.

The use of pesticides in agricultural activities has increased significantly during the last decades. Several studies have reported the health damage that results from exposure to pesticides. In Mexico, hundreds of communities depend economically on agricultural activities. The participation of minors in this type of activity and their exposure to pesticides represents a potential public health problem. A cross-sectional study was conducted, in which urine samples (first-morning urine) were taken from children under 15 years of age in both communities. A total of 281 urine samples obtained in both communities were processed for the determination of pesticides with high-performance liquid chromatography together with tandem mass spectrometry. In 100% of the samples, at least two pesticides of the 17 reported in the total samples were detected. The presence of malathion, metoxuron, and glyphosate was remarkable in more than 70% of the cases. Substantial differences were detected regarding the other compounds. It is necessary to carry out long-term studies to determine the damage to health resulting from this constant exposure and to inform the health authorities about the problem in order to implement preventive measures.

Global plastics production has reached 380 million metric tons in 2015, with around 40% used for packaging. Plastic packaging is diverse and made of multiple polymers and numerous additives, along with other components, such as adhesives or coatings. Further, packaging can contain residues from substances used during manufacturing, such as solvents, along with non-intentionally added substances (NIAS), such as impurities, oligomers, or degradation products. To characterize risks from chemicals potentially released during manufacturing, use, disposal, and/or recycling of packaging, comprehensive information on all chemicals involved is needed. Here, we present a database of Chemicals associated with Plastic Packaging (CPPdb), which includes chemicals used during manufacturing and/or present in final packaging articles. The CPPdb lists 906 chemicals likely associated with plastic packaging and 3377 substances that are possibly associated. Of the 906 chemicals likely associated with plastic packaging, 63 rank highest for human health hazards and 68 for environmental hazards according to the harmonized hazard classifications assigned by the European Chemicals Agency within the Classification, Labeling and Packaging (CLP) regulation implementing the United Nations' Globally Harmonized System (GHS). Further, 7 of the 906 substances are classified in the European Union as persistent, bioaccumulative, and toxic (PBT), or very persistent, very bioaccumulative (vPvB), and 15 as endocrine disrupting chemicals (EDC). Thirty-four of the 906 chemicals are also recognized as EDC or potential EDC in the recent EDC report by the United Nations Environment Programme. The identified hazardous chemicals are used in plastics as monomers, intermediates, solvents, surfactants, plasticizers, stabilizers, biocides, flame retardants, accelerators, and colorants, among other functions. Our work was challenged by a lack of transparency and incompleteness of publicly available information on both the use and toxicity of numerous substances. The most hazardous chemicals identified here should be assessed in detail as potential candidates for substitution.

STUDY QUESTION/OBJECTIVE:Are early-pregnancy urinary bisphenol and phthalate metabolite concentrations associated with placental function markers, blood pressure (BP) trajectories during pregnancy and risk of gestational hypertensive disorders? SUMMARY ANSWER/UNASSIGNED:Early-pregnancy bisphenols and phthalate metabolites were not consistently associated with maternal BP changes or gestational hypertensive disorders, but subclinical, statistically significant associations with placental angiogenic markers and placental hemodynamics were identified. WHAT IS KNOWN ALREADY/UNASSIGNED:In vitro studies suggest that bisphenols and phthalate metabolites may disrupt early placental development and affect the risk of gestational hypertensive disorders. Previous studies investigating effects of bisphenols and phthalate metabolites on gestational hypertensive disorders reported inconsistent results and did not examine placental function or BP throughout pregnancy. STUDY DESIGN, SIZE, DURATION/UNASSIGNED:In a population-based prospective cohort study, bisphenol and phthalate metabolite concentrations were measured in a spot urine sample in early pregnancy among 1396 women whose children participated in postnatal follow-up measurements. PARTICIPANTS/MATERIALS, SETTING, METHODS/UNASSIGNED:After exclusion of women without any BP measurement or with pre-existing hypertension, 1233 women were included in the analysis. Urinary bisphenol and phthalate metabolite concentrations were measured in early-pregnancy [median gestational age 13.1 weeks, inter-quartile range 12.1-14.5]. Molar sums of total bisphenols and of low molecular weight phthalate, high molecular weight (HMW) phthalate, di-2-ethylhexylphthalate, and di-n-octylphthalate metabolites were calculated. Placental angiogenic markers (placental growth factor (PlGF), soluble fms-like tyrosine kinase (sFlt)-1), placental hemodynamic function measures (umbilical artery pulsatility index (PI), uterine artery resistance index (RI), notching and placental weight), and maternal BP were measured in different trimesters. Information on gestational hypertensive disorders was obtained from medical records. MAIN RESULTS AND THE ROLE OF CHANCE/UNASSIGNED:Each log unit increase in HMW phthalate metabolites was associated with a 141.72 (95% CI: 29.13, 373.21) higher early pregnancy sFlt-1/PlGF ratio (range in total sample 9-900). This association was driven by mono-[(2-carboxymethyl)hexyl]phthalate. In the repeated measurements regression models, each log unit increase in bisphenol A was associated with a 0.15 SD (95% CI: 0.03, 0.26) higher intercept and -0.01 SD (95% CI: -0.01, -0.00) decreasing slope of the umbilical artery PI Z-score and a -1.28 SD (95% CI: -2.24, -0.33) lower intercept and 0.06 SD (95% CI: 0.02, 0.11) increasing slope of the uterine artery RI Z-score. These associations remained significant after Bonferroni correction. Early-pregnancy bisphenols or phthalate metabolites showed no consistent associations with any other outcome. LIMITATIONS, REASONS FOR CAUTION/UNASSIGNED:Information on a large number of potential confounders was available but was partly self-reported. Bisphenols and phthalate metabolites, which typically have a half-life of 24-48 h, were measured via single spot urine samples in early-pregnancy. In addition, at the current sample size, the study was powered to detect an odds ratio of 1.57 for gestational hypertension and 1.78 for pre-eclampsia, but was underpowered to perform multivariable analyses for these outcomes. Further studies combining data from different cohorts may be necessary to increase power. These limitations are possible sources of non-differential misclassification leading to bias toward the null. WIDER IMPLICATIONS OF THE FINDINGS/UNASSIGNED:Bisphenols and phthalate metabolites were not associated with longitudinal changes in BP in pregnancy in our low-risk population. The observed subclinical associations of phthalates with the sFlt-1/PlGF ratio and of bisphenol A with placental hemodynamics may contribute to adverse pregnancy outcomes. Our results are therefore more supportive of an association of early pregnancy bisphenols and phthalate metabolites with risk for pre-eclampsia than with gestational hypertension. STUDY FUNDING/COMPETING INTEREST(S)/UNASSIGNED:This analysis was supported by Grant (ES022972) from the National Institutes of Health, USA. The content is solely the responsibility of the authors and does not represent the official views of the National Institutes of Health. The authors report no conflicts of interest.

Perfluoroalkyl substances (PFAS) may have been released during the collapse of the World Trade Center (WTC) on 9/11. Evidence suggests PFAS can cross the placental barrier in humans and cause harm to the developing fetus; however, no studies have measured PFAS in mothers exposed to the WTC disaster during pregnancy. We measured PFAS in maternal plasma (n = 48) or cord blood (n = 231) from pregnant women in the Columbia University WTC birth cohort, enrolled between December 13, 2001 and June 26, 2002 at one of three hospitals located near the WTC site. In order to maximize sample size, we used a linear regression to transform the 48 maternal plasma samples to cord blood equivalents in our study; cord blood and transformed maternal plasma-to-cord blood samples were then analyzed together. We evaluated the association between WTC exposure and PFAS concentrations using three exposure variables: 1) living/working within two miles of WTC; 2) living within two miles of WTC regardless of work location; and 3) working but not living within two miles of WTC. Exposure was compared with those not living/working within two miles of WTC (reference group). Living/working within two miles of WTC was associated with 13% higher perfluorooctanoic acid (PFOA) concentrations compared with the reference group [GMR (95% CI): 1.13 (1.01, 1.27)]. The association was stronger when comparing only those who lived within two miles of WTC to the reference group [GMR (95% CI): 1.17 (1.03, 1.33)], regardless of work location. Our results provide evidence that exposure to the WTC disaster during pregnancy resulted in increases in PFAS concentrations, specifically PFOA. This work identifies a potentially vulnerable and overlooked population, children exposed to the WTC disaster in utero, and highlights the importance of future longitudinal studies in this cohort to investigate later life effects resulting from these early life exposures.

: media-1vid110.1542/5839981580001PEDS-VA_2018-0290Video Abstract OBJECTIVES: To determine the association of antibiotic use with weight outcomes in a large cohort of children.

BACKGROUND:Melamine and cyanuric acid, which are currently used in a variety of common consumer products and present in foods, have been implicated in the development of urolithiasis and acute kidney injury in Chinese children. To determine whether US children have measurable concentrations of these chemicals in their bodies and whether they are at greater risk of acute kidney injury, we measured melamine and cyanuric acid exposure in a cohort of US children and determined their relationship with markers of kidney injury. METHODS:We measured urinary melamine and cyanuric acid in a convenience sample of 109 children (4 months - 8 years) from Seattle, WA and New York City, NY using liquid chromatography with tandem mass spectrometry. We measured several urinary markers of kidney injury: fatty acid binding protein 3 (FABP3), kidney injury molecule 1 (KIM1), neutrophil gelatinase-associated lipocalin (NGAL) using Luminex xMAP methods, and urine urea was measured using standard laboratory methods. We described urinary melamine and cyanuric acid concentrations and assessed predictors of the exposures. We used multivariable linear regression to assess relationships between melamine/cyanuric acid and kidney injury markers in unadjusted and adjusted (creatinine, age, sex) analyses. RESULTS:Melamine and cyanuric acid were above the limit of detection (LOD) in 78% and 95% of all samples, respectively. The mean concentrations (SD) for melamine and cyanuric acid were 27.4 ng/ml (141.9 ng/ml) and 35.3 ng/ml (42.4 ng/ml). In unadjusted analyses, we observed statistically significant increases in the percentages of FABP3 and KIM1 in relation to a one log unit change in melamine and cyanuric acid, respectively. In adjusted analyses, we observed a 55% (95% CI 0, 141) increase in KIM1 in relation to a one log unit increase in cyanuric acid. CONCLUSIONS:US children have detectable concentrations of melamine and cyanuric acid in urine, and these concentrations are higher than those reported in children from other countries. This is a novel finding that improves upon previous exposure estimates using questionnaires only and suggests widespread exposure in the population. Cyanuric acid is associated with increased KIM 1 concentrations, suggesting kidney injury. Given the potential widespread exposure, future analyses should examine melamine and cyanuric acid in relation to chronic kidney disease and markers of kidney injury in a larger cohort that is representative of the general population.