Jessie P. Buckley

Consumer product exposures associated with urinary phthalate levels in pregnant women

Human phthalate exposure is ubiquitous, but little is known regarding predictors of urinary phthalate levels. To explore this, 50 pregnant women aged 18–38 years completed two questionnaires on potential phthalate exposures and provided a first morning void. Urine samples were analyzed for 12 phthalate metabolites. Associations with questionnaire items were evaluated via Wilcoxon tests and t-tests, and r-squared values were calculated in multiple linear regression models. Few measured factors were statistically significantly associated with phthalate levels. Individuals who used nail polish had higher levels of mono-butyl phthalate (P=0.048) than non-users. Mono-benzyl phthalate levels were higher among women who used eye makeup (P=0.034) or used makeup on a regular basis (P=0.004). Women who used cologne or perfume had higher levels of di-(2-ethylhexyl) phthalate metabolites. Household products, home flooring or paneling, and other personal care products were also associated with urinary phthalates. The proportion of variance in metabolite concentrations explained by questionnaire items ranged between 0.31 for mono-ethyl phthalate and 0.42 for mono-n-methyl phthalate. Although personal care product use may be an important predictor of urinary phthalate levels, most of the variability in phthalate exposure was not captured by our relatively comprehensive set of questionnaire items.

Predictors and variability of repeat measurements of urinary phenols and parabens in a cohort of Shanghai women and men.

Background: Exposure to certain phenols is ubiquitous because of their use in many consumer and personal care products. However, predictors of exposure have not been well characterized in most populations. Objectives: We sought to identify predictors of exposure and to assess the reproducibility of phenol concentrations across serial spot urine samples among Chinese adults. Methods: We measured 2,4-dichlorophenol, 2,5-dichlorophenol, butyl paraben, methyl paraben, propyl paraben, benzophenone-3, bisphenol A, and triclosan in urine collected during 1997–2006 from 50 participants of the Shanghai Women’s Health Study cohort and during 2002–2006 from 50 participants of the Shanghai Men’s Health Study cohort. We investigated predictors of concentrations using the Satterthwaite t-test, and assessed reproducibility among serial samples using intraclass correlation coefficients (ICCs) and Spearman correlation coefficients (SCCs). Results: Creatinine-corrected phenol concentrations were generally higher among women than men. Participants who had taken medicine within the previous 24 hr had higher concentrations of propyl paraben. Cigarette smoking was associated with lower concentrations of propyl and methyl parabens among men. Bottled water consumption was associated with higher bisphenol A, 2,4-dichlorophenol, and 2,5-dichlorophenol concentrations among women. Among men, reproducibility across serial samples was moderate for 2,4-dichlorophenol and 2,5-dichlorophenol (ICC = 0.54–0.60, SCC = 0.43–0.56), but lower for other analytes (ICC = 0.20–0.29). Reproducibility among women was low (ICC = 0.13–0.39), but increased when restricted to morning-only urine samples. Conclusions: Among these 100 Shanghai residents, urinary phenol concentrations varied by sex, smoking, and consumption of bottled water. Our results suggest that a single urine sample may be adequate for ranking exposure to the precursors of 2,4-dichlorophenol and 2,5-dichlorophenol among men and, under certain circumstances, among women. Citation: Engel LS, Buckley JP, Yang G, Liao LM, Satagopan J, Calafat AM, Matthews CE, Cai Q, Ji BT, Cai H, Engel SM, Wolff MS, Rothman N, Zheng W, Xiang YB, Shu XO, Gao YT, Chow WH. 2014. Predictors and variability of repeat measurements of urinary phenols and parabens in a cohort of Shanghai women and men. Environ Health Perspect 122:733–740; http://dx.doi.org/10.1289/ehp.1306830

Prenatal Phthalate Exposures and Body Mass Index Among 4- to 7-Year-old Children: A Pooled Analysis.

Background: Phthalates are hypothesized to cause obesity, but few studies have assessed whether prenatal phthalate exposures are related to childhood body mass index (BMI). Methods: We included 707 children from three prospective cohort studies enrolled in the US between 1998 and 2006 who had maternal urinary phthalate metabolite concentrations measured during pregnancy, and measures of weight and height at ages 4 to 7 years. We calculated age- and sex-standardized BMI z scores and classified children with BMI percentiles ≥85 as overweight/obese. We used mixed effects regression models to estimate associations between a 1 standard deviation increase in natural log phthalate metabolite concentrations and BMI z scores and overweight/obesity. We estimated associations in multiple metabolite models adjusted for confounders, and evaluated heterogeneity of associations by child’s sex, race/ethnicity, and cohort. Results: Mono-3-carboxypropyl phthalate concentrations were positively associated with overweight/obese status in children (odds ratio [95% credible interval] = 2.1 [1.2, 4.0]) but not with BMI z scores (&bgr; = −0.02 [−0.15, 0.11]). We did not observe evidence of obesogenic effects for other metabolites. However, monoethyl phthalate and summed di-(2-ethylhexyl) phthalate metabolites (∑DEHP) concentrations were inversely associated with BMI z scores among girls (monoethyl phthalate beta = −0.14 [−0.28, 0.00]; ∑DEHP beta = −0.12 [−0.27, 0.02]). Conclusions: Maternal urinary mono-3-carboxypropyl phthalate, a nonspecific metabolite of several phthalates, was positively associated with childhood overweight/obesity. Metabolites of diethyl phthalate and DEHP were associated with lower BMI in girls but not in boys, suggesting that prenatal exposures may have sexually dimorphic effects on physical development.

Evolving methods for inference in the presence of healthy worker survivor bias

Healthy worker survivor bias may occur in occupational studies due to the tendency for unhealthy individuals to leave work earlier, and consequently accrue less exposure, compared with their healthier counterparts. If occupational data are not analyzed using appropriate methods, this bias can result in attenuation or even reversal of the estimated effects of exposures on health outcomes. Recent advances in computing power, coupled with state-of-the-art statistical methods, have greatly increased the ability of analysts to control healthy worker survivor bias. However, these methods have not been widely adopted by occupational epidemiologists. We update the seminal review by Arrighi and Hertz-Picciotto (Epidemiology.1994; 5: 186-196) of the sources and methods to control healthy worker survivor bias. In our update, we discuss methodologic advances since the publication of that review, notably with a consideration of how directed acyclic graphs can inform the choice of appropriate analytic methods. We summarize and discuss methods for addressing this bias, including recent work applying g-methods to account for employment status as a time-varying covariate affected by prior exposure. In the presence of healthy worker survivor bias, g-methods have advantages for estimating less biased parameters that have direct policy implications and are clearly communicated to decision-makers.

Prenatal Phthalate Exposures and Childhood Fat Mass in a New York City Cohort.

Background: Experimental animal studies and limited epidemiologic evidence suggest that prenatal exposure to phthalates may be obesogenic, with potential sex-specific effects of phthalates having anti-androgenic activity. Objectives: We aimed to assess associations between prenatal phthalate exposures and childhood fat mass in a prospective cohort study. Methods: We measured phthalate metabolite concentrations in third-trimester maternal urine in a cohort of women enrolled in New York City between 1998 and 2002 (n = 404). Among 180 children (82 girls and 98 boys), we evaluated body composition using a Tanita scale at multiple follow-up visits between ages 4 and 9 years (363 total visits). We estimated associations of standard deviation differences or tertiles of natural log phthalate metabolite concentrations with percent fat mass using linear mixed-effects regression models with random intercepts for repeated outcome measurements. We assessed associations in multiple metabolite models and adjusted for covariates including prepregnancy body mass index, gestational weight gain, maternal smoking during pregnancy, and breastfeeding. Results: We did not observe associations between maternal urinary phthalate concentrations and percent body fat in models examining continuous exposures. Fat mass was 3.06% (95% CI: –5.99, –0.09%) lower among children in the highest tertile of maternal urinary concentrations of summed di(2-ethylhexyl) phthalate (ΣDEHP) metabolites than in children in the lowest tertile. Though estimates were imprecise, there was little evidence that associations between maternal urinary phthalate concentrations and percent fat mass were modified by child’s sex. Conclusions: Prenatal phthalate exposures were not associated with increased body fat among children 4–9 years of age, though high prenatal DEHP exposure may be associated with lower fat mass in childhood. Citation: Buckley JP, Engel SM, Mendez MA, Richardson DB, Daniels JL, Calafat AM, Wolff MS, Herring AH. 2016. Prenatal phthalate exposures and childhood fat mass in a New York City cohort. Environ Health Perspect 124:507–513; http://dx.doi.org/10.1289/ehp.1509788

Prenatal exposure to environmental phenols and childhood fat mass in the Mount Sinai Children's Environmental Health Study.

Early life exposure to endocrine disrupting chemicals may alter adipogenesis and energy balance leading to changes in obesity risk. Several studies have evaluated the association of prenatal bisphenol A exposure with childhood body size but only one study of male infants has examined other environmental phenols. Therefore, we assessed associations between prenatal exposure to environmental phenols and fat mass in a prospective birth cohort. We quantified four phenol biomarkers in third trimester maternal spot urine samples in a cohort of women enrolled in New York City between 1998 and 2002 and evaluated fat mass in their children using a Tanita scale between ages 4 and 9years (173 children with 351 total observations). We estimated associations of standard deviation differences in natural log creatinine-standardized phenol biomarker concentrations with percent fat mass using linear mixed effects regression models. We did not observe associations of bisphenol A or triclosan with childhood percent fat mass. In unadjusted models, maternal urinary concentrations of 2,5-dichlorophenol were associated with greater percent fat mass and benzophenone-3 was associated with lower percent fat mass among children. After adjustment, phenol biomarkers were not associated with percent fat mass. However, the association between benzophenone-3 and percent fat mass was modified by childs sex: benzophenone-3 concentrations were inversely associated with percent fat mass in girls (beta=-1.51, 95% CI=-3.06, 0.01) but not boys (beta=-0.20, 95% CI=-1.69, 1.26). Although we did not observe strong evidence that prenatal environmental phenols exposures influence the development of childhood adiposity, the potential antiadipogenic effect of benzophenone-3 in girls may warrant further investigation.

Seasonal modification of the association between temperature and adult emergency department visits for asthma: A case-crossover study

BackgroundThe objective of this study is to characterize the effect of temperature on emergency department visits for asthma and modification of this association by season. This association is of interest in its own right, and also important to understand because temperature may be an important confounder in analyses of associations between other environmental exposures and asthma. For example, the case-crossover study design is commonly used to investigate associations between air pollution and respiratory outcomes, such as asthma. This approach controls for confounding by month and season by design, and permits adjustment for potential confounding by temperature through regression modeling. However, such models may fail to adequately control for confounding if temperature effects are seasonal, since case-crossover analyses rarely account for interactions between matching factors (such as calendar month) and temperature.MethodsWe conducted a case-crossover study to determine whether the association between temperature and emergency department visits for asthma varies by season or month. Asthma emergency department visits among North Carolina adults during 2007–2008 were identified using a statewide surveillance system. Marginal as well as season- and month-specific associations between asthma visits and temperature were estimated with conditional logistic regression.ResultsThe association between temperature and adult emergency department visits for asthma is near null when the overall association is examined [odds ratio (OR) per 5 degrees Celsius = 1.01, 95% confidence interval (CI): 1.00, 1.02]. However, significant variation in temperature-asthma associations was observed by season (chi-square = 18.94, 3 degrees of freedom, p <0.001) and by month of the year (chi-square = 45.46, 11 degrees of freedom, p <0.001). ORs per 5 degrees Celsius were increased in February (OR = 1.06, 95% CI: 1.02, 1.10), July (OR = 1.16, 95% CI: 1.04, 1.29), and December (OR = 1.04, 95% CI: 1.01, 1.07) and decreased in September (OR = 0.92, 95% CI: 0.87, 0.97).ConclusionsOur empirical example suggests that there is significant seasonal variation in temperature-asthma associations. Epidemiological studies rarely account for interactions between ambient temperature and temporal matching factors (such as month of year) in the case-crossover design. These findings suggest that greater attention should be given to seasonal modification of associations between temperature and respiratory outcomes in case-crossover analyses of other environmental asthma triggers.

The burden of comedication among patients with inflammatory bowel disease.

Background:Polypharmacy is of growing concern in the chronically ill, including individuals with inflammatory bowel disease (IBD). The authors aimed to describe the prevalence and predictors of non-IBD medication use and to compare drug use among individuals with and without IBD. Methods:This cross-sectional study included members of health plans included in the Thomson Reuters MarketScan databases with continuous enrollment during 2009 and 2010. Patients with IBD were identified through diagnosis codes and IBD medication dispensings and matched to 5 individuals without IBD. The prevalences of dispensed prescriptions for analgesics (narcotics, nonnarcotics), psychiatric medications (anxiolytics/sedatives/hypnotics, antidepressants), and broad drug classes defined by the Anatomic Therapeutic Classification system were estimated. Predictors of non-IBD medication use and comparisons of drug use by IBD status were evaluated using logistic regression. Results:The prevalence of medication use was higher among patients with IBD than matched members of the general population for nearly every drug class examined, including narcotic analgesics (48.1% versus 34.1%), nonnarcotic analgesics (12.8% versus 8.1%), anxiolytics/sedatives/hypnotics (25.8% versus 16.7%), and antidepressants (28.3% versus 19.4%). Medicaid insurance, middle age, gastrointestinal surgery, Crohns disease, and increasing number of inpatient, and outpatient, and prescription events were significantly associated with analgesic and psychiatric medication use among patients with IBD. Psychiatric drug dispensings were more common among female IBD patients than male patients. Conclusions:Patients with IBD have increased medication use, particularly of analgesic and psychiatric drugs. IBD care providers should be aware of polypharmacy and its potential for drug interactions.

Occupational radon exposure and lung cancer mortality: estimating intervention effects using the parametric g-formula.

Background: Traditional regression analysis techniques used to estimate associations between occupational radon exposure and lung cancer focus on estimating the effect of cumulative radon exposure on lung cancer. In contrast, public health interventions are typically based on regulating radon concentration rather than workers’ cumulative exposure. Estimating the effect of cumulative occupational exposure on lung cancer may be difficult in situations vulnerable to the healthy worker survivor bias. Methods: Workers in the Colorado Plateau Uranium Miners cohort (n = 4,134) entered the study between 1950 and 1964 and were followed for lung cancer mortality through 2005. We use the parametric g-formula to compare the observed lung cancer mortality to the potential lung cancer mortality had each of 3 policies to limit monthly radon exposure been in place throughout follow-up. Results: There were 617 lung cancer deaths over 135,275 person-years of follow-up. With no intervention on radon exposure, estimated lung cancer mortality by age 90 was 16%. Lung cancer mortality was reduced for all interventions considered, and larger reductions in lung cancer mortality were seen for interventions with lower monthly radon exposure limits. The most stringent guideline, the Mine Safety and Health Administration standard of 0.33 working-level months, reduced lung cancer mortality from 16% to 10% (risk ratio = 0.67 [95% confidence interval = 0.61 to 0.73]). Conclusions: This work illustrates the utility of the parametric g-formula for estimating the effects of policies regarding occupational exposures, particularly in situations vulnerable to the healthy worker survivor bias.

Statistical approaches for estimating sex-specific effects in endocrine disruptors research

Background: When a biologic mechanism of interest is anticipated to operate differentially according to sex, as is often the case in endocrine disruptors research, investigators routinely estimate sex-specific associations. Less attention has been given to potential sexual heterogeneity of confounder associations with outcomes. When relationships of covariates with outcomes differ according to sex, commonly applied statistical approaches for estimating sex-specific endocrine disruptor effects may produce divergent estimates. Objectives: We discuss underlying assumptions and evaluate the performance of two traditional approaches for estimating sex-specific effects, stratification and product terms, and introduce a simple modeling alternative: an augmented product term approach. Methods: We describe the impact of assumptions regarding sexual heterogeneity of confounder relationships on estimates of sex-specific effects of the exposure of interest for three approaches: stratification, traditional product terms, and augmented product terms. Using simulated and applied examples, we demonstrate properties of each approach under a range of scenarios. Results: In simulations, sex-specific exposure effects estimated using the traditional product term approach were biased when confounders had sex-dependent associations with the outcome. Sex-specific estimates from stratification and the augmented product term approach were unbiased but less precise. In the applied example, the three approaches yielded similar estimates, but resulted in some meaningful differences in conclusions based on statistical significance. Conclusions: Investigators should consider sexual heterogeneity of confounder associations when choosing an analytic approach to estimate sex-specific effects of endocrine disruptors on health. In the presence of sex-dependent confounding, our augmented product term approach may be advantageous over stratification when there is prior knowledge available to fit reduced models or when investigators seek an automated test for effect measure modification. https://doi.org/10.1289/EHP334