Faculty Bibliography

Fetal growth is affected by exposure to both prenatal stress and environmental contaminants. The attacks on the World Trade Center (WTC) resulted in exposure to chemicals and psychological stress amongst New York City residents. We measured prenatal maternal stress and exposure to persistent organic pollutants (polybrominated diphenyl ethers, polychlorinated biphenyls, and polychlorinated dibenzo-p-dioxins (PCDDs)) in 108 participants from a Columbia University WTC birth cohort. Principal component (PC) analyses were conducted to characterize the mixture of exposure to the three groups of chemicals. We evaluated the associations between geographical exposures (proximity to the WTC disaster) and both chemical exposures (PCs) and stress (demoralization). We then evaluated the effect these exposures (PCs and stress) had on previously reported associations between geographical WTC exposure and birth outcomes (birth weight and birth length) in this study population to understand their individual roles in the observed associations. Geographical exposure via proximity to the WTC was associated with the PC reflecting higher PCDD exposure (PC3) (β = 0.60, 95% CI: 0.03, 1.18 for living/working within 2 miles of the WTC; and β = 0.73, 95% CI = 0.08, 1.38 for living within 2 miles of WTC). Previously reported reductions in birth weight and length associated with WTC proximity (β = -215.2, 95% CI: -416.2, -14.3 and β = -1.47, 95% CI: -2.6, -0.34, respectively) were attenuated and no longer significant for birth weight (β = -156.4, 95% CI: -358.2, 45.4) after adjusting for PC3, suggesting that PCDDs may act as partial mediators in this previously observed association. The results of this study can help focus future research on the long-term health effects of these prenatally exposed populations.

RATIONALE/BACKGROUND:Asthma and obesity often co-occur. It has been hypothesized that asthma may contribute to childhood obesity onset. OBJECTIVES/OBJECTIVE:To determine if childhood asthma is associated with incident obesity and examine the role of asthma medication in this association. METHODS:We studied 8,716 children between ages 6 and 18.5 years who were nonobese at study entry participating in 18 US cohorts of the Environmental influences on Child Health Outcomes program (among 7,299 children with complete covariate data mean [SD] study entry age = 7.2 [1.6] years and follow up = 5.3 [3.1] years). MEASUREMENTS AND MAIN RESULTS/RESULTS:We defined asthma based on caregiver report of provider diagnosis. Incident obesity was defined as the first documented body mass index ≥95th percentile for age and sex following asthma status ascertainment. Over the study period, 26% of children had an asthma diagnosis and 11% developed obesity. Cox proportional hazards models with sex-specific baseline hazards were fitted to assess the association of asthma diagnosis with obesity incidence. Children with asthma had a 23% (95% confidence intervals [CI] = 4, 44) higher risk for subsequently developing obesity compared with those without asthma. A novel mediation analysis was also conducted to decompose the total asthma effect on obesity into pathways mediated and not mediated by asthma medication use. Use of asthma medication attenuated the total estimated effect of asthma on obesity by 64% (excess hazard ratios = 0.64; 95% CI = -1.05, -0.23). CONCLUSIONS:This nationwide study supports the hypothesis that childhood asthma is associated with later risk of obesity. Asthma medication may reduce this association and merits further investigation as a potential strategy for obesity prevention among children with asthma.

OBJECTIVE:To estimate the prevalence of perinatal cannabis use (ie, before and/or during pregnancy); document the frequency, modes, and motivations for use; and identify predictors of perinatal cannabis use. METHODS:Six states in the Pregnancy Risk Assessment Monitoring System, a state-specific, population-based surveillance system, administered a supplemental questionnaire on perinatal cannabis use in 2016-2018. Women with live births were surveyed 2-6 months postpartum about behaviors ≤3 months preconception and during pregnancy. Demographic, psychosocial, and behavioral characteristics were examined in relation to perinatal cannabis use using multinomial regression models. Those who: (1) never used cannabis, (2) only used in preconception period, and (3) used in both preconception and prenatal periods were compared. RESULTS:Among 6428 respondents, 379 (5.8%) used cannabis preconceptionally only and 466 (4.4%) used in both the preconception and prenatal periods. Among those using prenatally, most reported smoking as their single mode (87.1%), with the two most common reasons being stress (83.8%) and nausea/vomiting (79.2%). Marital status, race/ethnicity, socioeconomic status, parity, and cigarette and alcohol use were significantly associated with perinatal cannabis use. Single (vs partnered) women were more likely to use cannabis prenatally (odds ratio = 2.4, 95% confidence interval: 1.5, 3.9) and non-Hispanic Black (vs White) women were less likely to use prenatally (odds ratio = 0.4, 95% confidence interval: 0.2, 0.8). CONCLUSIONS:Using a population-based sample of US births in six states, several demographic, psychosocial, and behavioral characteristics were identified in relation to perinatal cannabis use. These data are valuable for counseling in prenatal care and investigations of health effects.

While definitions vary, endocrine-disrupting chemicals (EDCs) have two fundamental features: their disruption of hormone function and their contribution to disease and disability. The unique vulnerability of children to low-level EDC exposures has eroded the notion that only the dose makes the thing a poison, requiring a paradigm shift in scientific and policy practice. In this review, we discuss the unique vulnerability of children as early as fetal life and provide an overview of epidemiological studies on programming effects of EDCs on neuronal, metabolic, and immune pathways as well as on endocrine, reproductive, and renal systems. Building on this accumulating evidence, we dispel and address existing myths about the health effects of EDCs with examples from child health research. Finally, we provide a list of effective actions to reduce exposure, and subsequent harm that are applicable to individuals, communities, and policy-makers. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 62 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

CONTEXT/BACKGROUND:Accelerating evidence of endocrine-related morbidity has raised alarm about the ubiquitous use of phthalates in the human environment, but studies have not directly evaluated mortality in relation to these exposures. OBJECTIVES/OBJECTIVE:To evaluate associations of phthalate exposure with mortality, and quantify attributable mortality and lost economic productivity in 2013-4 among 55-64 year olds. DESIGN/METHODS:This nationally representative cohort study included 5303 adults aged 20 years or older who participated in the US National Health and Nutrition Examination Survey 2001-2010 and provided urine samples for phthalate metabolite measurements. Participants were linked to mortality data from survey date through December 31, 2015. Data analyses were conducted in July 2020. MAIN OUTCOME MEASURES/METHODS:Mortality from all causes, cardiovascular disease, and cancer. RESULTS:Multivariable models identified increased mortality in relation to high-molecular weight (HMW) phthalate metabolites, especially those of di-2-ethylhexylphthalate (DEHP). Hazard ratios (HR) for continuous HMW and DEHP metabolites were 1.14 (95% CI 1.06-1.23) and 1.10 (95% CI 1.03-1.19), respectively, with consistently higher mortality in the third tertile (1.48, 95% CI 1.19-1.86; and 1.42, 95% CI 1.13-1.78). Cardiovascular mortality was significantly increased in relation to a prominent DEHP metabolite, mono-(2-ethyl-5-oxohexyl)phthalate. Extrapolating to the population of 55-64 year old Americans, we identified 90,761-107,283 attributable deaths and $39.9-47.1 billion in lost economic productivity. CONCLUSIONS:In a nationally representative sample, phthalate exposures were associated with all-cause and cardiovascular mortality, with societal costs approximating $39 billion/year or more. While further studies are needed to corroborate observations and identify mechanisms, regulatory action is urgently needed.

Rapidly accumulating evidence supports the role of synthetic chemicals as obesogens and cardiometabolic risks. This presentation provides an overview of the latest evidence, safe and simple steps for prevention, and business case for policy intervention

Prenatal exposure to nonpersistent chemicals such as phthalates, bisphenols, and organophosphate (OP) pesticides is ubiquitous and occurs in mixtures. So far, epidemiological studies investigating neurodevelopmental consequences of these exposures have mainly been restricted to single-pollutant models. Thus, we studied the association between prenatal exposure to nonpersistent chemical mixtures and child IQ and emotional and behavioral problems. Data came from 782 mother-child pairs. Eleven phthalate, one bisphenol, and five OP pesticide urinary exposure biomarkers were measured three times during pregnancy and averaged. Nonverbal IQ, internalizing and attention problems, aggressive behavior, and autistic traits were assessed at child age 6 years. We used quantile g-computation to estimate the change in each outcome per quartile increase in all chemicals within the mixture. Higher exposure to the mixture was associated with lower nonverbal IQ (-4.0 points (95%CI = -7.0, -1.0), -5.5 points (95%CI = -10.2, -0.9), and -4.6 points (95%CI = -10.8, 1.5) for the second, third, and fourth quartile, respectively, compared to the first quartile). These results were mainly driven by the phthalate mixture. No association was observed with emotional and behavioral problems. Prenatal exposure to nonpersistent chemical mixtures was associated with lower nonverbal IQ in children. Exposure to chemical mixtures during gestation is universal and may impact neurodevelopment.

Although human exposure to microplastics (MPs) and the health effects thereof are a global concern, little is known about the magnitude of exposure. In this study, we quantitatively determined the concentrations of polyethylene terephthalate (PET) and polycarbonate (PC) MPs in three meconium and six infant and 10 adult feces samples collected from New York State. PET and PC MPs were found in some meconium samples (at concentration ranges from below the limit of quantification [<LOQ] to 12,000 and <LOQ-110 ng/g dry weight, respectively) and all infant stool specimens (PET: 5700-82,000 ng/g, median, 36,000 ng/g; PC: 49-2100 ng/g, median, 78 ng/g). They were also found in most (PET) or all (PC) adult stool samples but at concentrations an order of magnitude lower than in infants for PET MPs (<LOQ-16,000 ng/g, median, 2600 ng/g). The estimated mean daily exposures from the diet of infants to PET and PC MPs were 83,000 and 860 ng/kg body weight per day, respectively, which were significantly higher than those of adults (PET: 5800 ng/kg-bw/day; PC: 200 ng/kg-bw/d). Our study suggests that infants are exposed to higher levels of MPs than adults.

Over the past several decades, scientific consensus has grown around the concept and evidence for human health impacts from exposure to endocrine disrupting chemicals (EDCs). A series of publications have now demonstrated considerable economic costs of EDC exposure-induced adverse health outcomes. This research has suggested economic burdens in the hundreds of billions, even considering only a small subset of EDCs and health. As of yet, regulatory efforts and policies to protect and decrease human exposure to most EDCs have been insufficient and have not kept pace with the science. Given the overwhelming scientific evidence, referenced throughout this collection, as well as the economic costs of inaction, described here, regulations are clearly needed. The EU and some other countries have taken promising steps towards protective regulation of EDCs, though the response of the US and many other countries has been limited or altogether lacking. Regulatory bodies that have and continue to apply risk-based approaches to regulating EDCs have also failed to consider the complete economic impacts of EDC-related health impacts. In this chapter, we will discuss broad strategies taken to regulate EDCs, examine the approaches currently taken to regulate EDCs in a global context (discussing the strengths and weaknesses of these regulations), discuss the economic costs of EDC exposures (detailing where consideration of health and economic costs could improve regulations), and discuss next steps and novel approaches to adapting existing regulatory frameworks to this class of chemicals.