Faculty Bibliography

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.

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.

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.

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.

Background: suPAR is an inflammatory mediator that has been linked to the pathogenesis of FSGS and progression of chronic kidney disease in children and adults. Overexpression of suPAR leads to reduced nephron development in preclinical models. This study was designed to measure suPAR in pregnant women to determine the range of fetal exposure to this molecule and its potential influence on antenatal human kidney growth.
Method(s): Pregnant women enrolled in the Children's Health and Environment Study (CHES) provided serum samples obtaining during 1-3 trimesters. Clinical information was obtained from the electronic health record. suPAR levels were determined by ELISA (Virogates, Copenhagen, Denmark). Data are presented as mean+/-SD. Results were analyzed by Pearson correlation and ANOVA.
Result(s): 515 mothers were studied, age 31+/-6 yr, and racial distribution 44% Caucasian, 7% African American, 9 % Asian, and 41% other/unspecified. 46% of the women were Hispanic. 29% had completed a high school education or less and 28% had an annual income <$50,000. There were 464 livebirths, 50.4% girls. The serum suPAR levels (mean, SD, minimum, maximum) are summarized in the Table. The suPAR levels in the subgroup of women who provided more than one sample during pregnancy were closely correlated (r=0.79-0.94, P<0.0001)). The decline in serum suPAR levels from trimester 1 to 3 was highly significant (P<0.001).
Conclusion(s): Maternal suPAR levels are detectable throughout pregnancy but decline from trimester 1 to 3. The levels are highly correlated and steady during the course of pregnancy in an individual woman. There is more than a 10-fold range in suPAR concentration which may contribute to the biological variation in nephron number at birth. Follow-up assessment in the infants will be performed in the prospective Environmental Influences on Child Health Outcomes (ECHO) cohort study. (Table Presented)

Background: Environmental chemical exposures are linked to oxidative stress and kidney injury in children and adults. This applies to short-lived organic compounds such as bisphenol A and phthalates and persistent synthetic chemicals such as perfluoroalkyl acids (PFAAs). Most investigations to date have been conducted in developed countries with few data about environmental chemical exposures in children living in Africa.
Method(s): Clinical and laboratory data about pediatric patients enrolled in the H3 Africa observational cohort study including age, gender, BMI, serum creatinine, eGFR, proteinuria were collected. Serum samples that had been collected at enrollment were retrieved from the Biorepository and analyzed for PFAAs and polybrominated diphenyl ethers (PBDEs) and DDE presticides using established methods. Proteinuria was assessed in a first morning urine sample. Results are presented as mean+/-SD.
Result(s): 86 patients with CKD (41 M:45 F), age 12.6+/-2.6 yr old, were included in this nested case control study. The eGFR was 75+/-4 and the albumin:creatinine ratio was 65+/-186. The chemical exposures are summarized in the Table. There was no association between exposure (log of serum concentration) to PFAAs and proteinuria. However, controlling for age, gender, and BMI, there was an inverse relationship between eGFR and exposure to PFNA, -21.2 [95% CI:-41.6 -0.8] and PFDA -18.3 [95% CI:-35.3 --1.3] ml/min/log unit increase in exposure and a trend towards a similar effect for PFOS. PBDE/DDEs were detected in a small fraction of children and because of small sample size associations with effect markers were not made
Conclusion(s): PFAA exposure is substantially lower in H3 Africa participants than in healthy US children, age 12-19 enrolled in NHANES 2003-2010. However, even at these lower levels of exposure there was an adverse association between select PFAAs and GFR. These studies indicate the feasibility of measuring environmental chemical exposure in developing countries. The impact of these chemical exposures on kidney function will require larger cohorts of children followed for more extended periods of time

: 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.

Substantial effort has been devoted to explaining secular trends in childhood obesity and metabolic risks to unhealthy diet and physical activity. While some studies have suggested these factors may play a role in the obesity epidemic, even these studies have only been able to conclude that these factors have a moderate role. Given that a single-generation transformation in the human genome is even more unlikely to have transformed susceptibility to excess weight gain in early life, we are left with the reality that environmental influences represent important risks for obesity and dysmetabolism. In contrast to diet and physical activity, which can require intensive attention, effort and costs to modify through behavioral and other interventions, government action can fundamentally transform the environment and prevent disease and disability. The costs of regulations to limit environmental obesogens can also be much lower than the benefits to society.