Faculty Bibliography

Declining life expectancy and increasing all-cause mortality in the United States have been associated with unhealthy behaviors, socioecological factors, and preventable disease. A growing body of basic science, clinical research, and population health evidence points to the benefits of healthy behaviors, environments and policies to maintain health and prevent, treat, and reverse the root causes of common chronic diseases. Similarly, innovations in research methodologies, standards of evidence, emergence of unique study cohorts, and breakthroughs in data analytics and modeling create new possibilities for producing biomedical knowledge and clinical translation. To understand these advances and inform future directions research, The Lifestyle Medicine Research Summit was convened at the University of Pittsburgh on December 4-5, 2019. The Summit's goal was to review current status and define research priorities in the six core areas of lifestyle medicine: plant-predominant nutrition, physical activity, sleep, stress, addictive behaviors, and positive psychology/social connection. Forty invited subject matter experts (1) reviewed existing knowledge and gaps relating lifestyle behaviors to common chronic diseases, such as cardiovascular disease, diabetes, many cancers, inflammatory- and immune-related disorders and other conditions; and (2) discussed the potential for applying cutting-edge molecular, cellular, epigenetic and emerging science knowledge and computational methodologies, research designs, and study cohorts to accelerate clinical applications across all six domains of lifestyle medicine. Notably, federal health agencies, such as the Department of Defense and Veterans Administration have begun to adopt "whole-person health and performance" models that address these lifestyle and environmental root causes of chronic disease and associated morbidity, mortality, and cost. Recommendations strongly support leveraging emerging research methodologies, systems biology, and computational modeling in order to accelerate effective clinical and population solutions to improve health and reduce societal costs. New and alternative hierarchies of evidence are also be needed in order to assess the quality of evidence and develop evidence-based guidelines on lifestyle medicine. Children and underserved populations were identified as prioritized groups to study. The COVID-19 pandemic, which disproportionately impacts people with chronic diseases that are amenable to effective lifestyle medicine interventions, makes the Summit's findings and recommendations for future research particularly timely and relevant.

The authors would like to update some important data in the manuscript. In Table 4, the pesticide means were reported in µg/mL, which is incorrect. The correct units are ng/mL (nanograms/milliliter). The same typographical inaccuracy applies for data in the fourth paragraph of the discussion (with minimal values of 0.0020 µg/mL and maximal values of 2.63 µg/mL), where the correct units are also ng/mL [1]. [...].

BACKGROUND:Insufficient or excessive gestational weight gain are associated with increased risks of adverse birth and childhood outcomes. Increasing evidence suggests that exposure to bisphenols and phthalates may disrupt hormonal pathways and thereby influence gestational weight gain. OBJECTIVE:To examine the associations of early and mid-pregnancy bisphenol and phthalate urine concentrations with gestational weight gain. METHODS:In a population-based prospective cohort study among 1,213 pregnant women, we measured early and mid-pregnancy bisphenol and phthalate urine concentrations. Maternal anthropometrics before pregnancy were obtained by questionnaire and repeatedly measured at our research center during pregnancy. We used linear and logistic regressions to evaluate the associations of bisphenols and phthalates with total and period-specific gestational weight gain. RESULTS:Higher maternal total bisphenols and bisphenol S were associated with a lower total gestational weight gain at nominal level. Stratification by body mass index group showed that higher total bisphenols and bisphenol S were associated with lower total gestational weight gain specifically in normal weight women (respectively -509 g [95% CI -819, -198] and -398 g [95% CI -627, -169]). Each log unit increase in early pregnancy total bisphenol and bisphenol A urine concentrations were associated with lower mid- to late pregnancy gestational weight gain in the whole group (effect estimates -218 g/log unit increase [95% CI -334, -102] and -132 g/log unit increase [95% CI -231, -34], respectively). These associations were independent of mid-pregnancy compounds. Mid-pregnancy bisphenols and phthalates concentrations were not associated with gestational weight gain. DISCUSSION/CONCLUSIONS:Higher maternal bisphenol urine concentrations in early pregnancy may lead to reduced gestational weight in second half of pregnancy. Further research is needed to assess the effects of maternal bisphenols and phthalates urine concentrations on placental and fetal growth and development.

Endocrine disrupting chemicals are known to cause neurodevelopmental toxicity through direct and indirect pathways. In this study we used data from the National Health and Nutrition Examination Surveys, along with known exposure-disease relationships, to quantify the intellectual disability burden attributable to in utero exposure to polybrominated diphenyl ethers (PBDEs), organophosphates, and methylmercury and early life exposure to lead. We also estimated the cost of the IQ points lost and cases of intellectual disability. PBDE exposure was the greatest contributor to intellectual disability burden, resulting in a total of 162 million IQ points lost and over 738,000 cases of intellectual disability. This was followed by lead, organophosphates, and methylmercury. From 2001 to 2016, IQ loss from PBDEs, methylmercury, and lead have decreased or remained stagnant. Organophosphate exposure measurements were only available up to 2008 but did show an increase in organophosphate-attributable IQ loss. Although most of these trends show benefit for children's neurodevelopmental health, they may also point towards the use of potentially harmful substitutions for chemicals that are being phased out.

The goal of this study was to assess biomarkers of exposure to glyphosate and assess potential associations with renal function in children. Glyphosate is used ubiquitously in agriculture worldwide. While previous studies have indicated that glyphosate may have nephrotoxic effects, few have examined potential effects on kidney function in children. We leveraged three cohorts across different phases of child development and measured urinary levels of glyphosate. We evaluated associations of glyphosate with three biomarkers of kidney injury: albuminuria (ACR), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury marker 1 (KIM-1). Multivariable regression analyses examined associations of glyphosate with kidney injury biomarkers controlling for covariates. We identified glyphosate in 11.1% of the total participants. The herbicide was detected more frequently in the neonate population (30%). Multivariable regression models failed to identify significant associations of log-transformed glyphosate with any of the kidney injury biomarkers, controlling for covariates age, sex, and maternal education. While we confirm detectability of glyphosate in children's urine at various ages and stages of life, there is no evidence in this study for renal injury in children exposed to low levels of glyphosate. Further studies of larger sample size are indicated to better understand putative deleterious effects of the herbicide after different levels of exposure.

BACKGROUND:The Global Burden of Disease (GBD) study, coordinated by the Institute for Health Metrics and Evaluation (IHME), produces influential, data-driven estimates of the burden of disease and premature death due to major risk factors. Expanded quantification of disease due to environmental health (EH) risk factors, including climate change, will enhance accuracy of GBD estimates, which will contribute to developing cost-effective policies that promote prevention and achieving Sustainable Development Goals. OBJECTIVES/OBJECTIVE:We review key aspects of the GBD for the EH community and introduce the Global Burden of Disease-Pollution and Health Initiative (GBD-PHI), which aims to work with IHME and the GBD study to improve estimates of disease burden attributable to EH risk factors and to develop an innovative approach to estimating climate-related disease burden-both current and projected. METHODS:We discuss strategies for improving GBD quantification of specific EH risk factors, including air pollution, lead, and climate change. We highlight key methodological challenges, including new EH risk factors, notably evidence rating and global exposure assessment. DISCUSSION/CONCLUSIONS:A number of issues present challenges to the scope and accuracy of current GBD estimates for EH risk factors. For air pollution, minimal data exist on the exposure-risk relationships associated with high levels of pollution; epidemiological studies in high pollution regions should be a research priority. For lead, the GBD's current methods do not fully account for lead's impact on neurodevelopment; innovative methods to account for subclinical effects are needed. Decisions on inclusion of additional EH risk-outcome pairs need to be guided by findings of systematic reviews, the size of exposed populations, feasibility of global exposure estimates, and predicted trends in exposures and diseases. Neurotoxicants, endocrine-disrupting chemicals, and climate-related factors should be high priorities for incorporation into upcoming iterations of the GBD study. Enhancing the scope and methods will improve the GBD's estimates and better guide prevention policy. https://doi.org/10.1289/EHP5496.

Bisphenol A (BPA) has been recognized as an endocrine disrupting chemical and identified as an obesogen. Although once ubiquitous, human exposure to BPA has been declining owing to its substitution with other bisphenols. Two structurally similar substitutes, bisphenol S (BPS) and bisphenol F (BPF), have raised similar concerns, although fewer studies have been conducted on these newer derivatives. We used data from the US National Health and Nutrition Examination Surveys from 2013 to 2016 to evaluate associations between BPA, BPS, and BPF and body mass outcomes among children and adolescents aged 6 to 19 years. Concentrations of BPA, BPS, and BPF were measured in spot urine samples using HPLC with tandem mass spectrometry. General obesity was defined as ≥95th percentile of the age- and sex-standardized body mass index (BMI) z-scores according to the 2000 US norms. Abdominal obesity was defined as a waist circumference/height ratio of ≥0.5. BPA, BPS, and BPF were detected in 97.5%, 87.8%, and 55.2% of urine samples, respectively. Log-transformed urinary BPS concentrations were associated with an increased prevalence of general obesity (OR, 1.16; 95% CI, 1.02 to 1.32) and abdominal obesity (OR, 1.13; 95% CI, 1.02 to 1.27). BPF detection (vs not detected) was associated with an increased prevalence of abdominal obesity (OR, 1.29; 95% CI, 1.01 to 1.64) and continuous BMI z-score (β = 0.10; 95% CI, 0.01 to 0.20). BPA and total bisphenols were not statistically significantly associated with general obesity, abdominal obesity, or any body mass outcome. These results suggest that BPA substitute chemicals are correlated with obesity in contemporary children.

Prenatal exposure to phenolic compounds, widely used in many consumer products, can alter lung development and increase the risk of respiratory disorders in the offspring. However, evidence is scarce and mostly focused on bisphenol-A (BPA), although there are other substitutes that could also interfere with the developing respiratory system. We aim to estimate the association between exposure to 5 phenols during pregnancy (BPA, BPAF, BPB, BPF, and BPS) and lung function, wheeze, and asthma in school-age children. We included 2685 mother-child pairs from 8 European birth cohorts. Phenols concentrations were determined in urinary maternal samples collected during pregnancy (1999-2010). Between 6 and 10 years of age, spirometry was performed, and wheeze and asthma were assessed from questionnaires. Adjusted multivariable linear regression and logistic regression models were used to assess the associations. We performed meta-analyses of cohort-specific estimates. We observed widespread prenatal BPA exposure with 79% of the samples above detectable limits; the other phenols were detected in fewer samples. Median BPA concentrations ranged from 1.04 to 9.54 ng/g of creatinine. Increasing BPA concentrations during pregnancy tended to be associated with lower FVC and FEV1 and were associated with increased odds of wheezing between ages 6 and 10 years (adjusted odds ratio=1.09; 95% CI=0.96, 1.24), but notwith asthma. Final results including associations of the other phenols with respiratory outcomes including wheezing patterns from birth will be presented. Preliminary results showed that prenatal exposure to BPA might increase the odds of wheezing in school-age children