Faculty Bibliography

Pregnant women are exposed to various chemicals, including endocrine-disrupting chemicals (EDCs) such as phthalates and bisphenols. Increasing evidence suggests that early life exposures to phthalates and bisphenols may contribute to cardiometabolic risks. The aim of this narrative review was to summarize current knowledge of the effects of fetal and childhood exposure to phthalates and bisphenols on child growth and child cardiometabolic outcomes and the effects on maternal outcomes. In total, 54 studies were identified and included. The majority of studies found effects of phthalates and bisphenols on maternal, child growth, and cardiometabolic outcomes. Currently results suggest that early life exposure to phthalates and bisphenols may have a substantial influence on perinatal and postnatal cardiometabolic programming. In a large part of the investigated outcomes studies show contradictory results. However, the majority of the existing evidence is based on non-cohort studies with single samples neglecting time-variant effects and complicating conclusions regarding causal inference. More studies are needed investigating the mechanisms and its potential interactions.

BACKGROUND: A previous analysis examined the contribution of endocrine disruptor exposures (endocrine-disrupting chemicals, EDCs) to adult diabetes, but was limited to effects of phthalates in middle-aged women and did not simultaneously examine multiple EDCs which are known to coexist in the environment. We therefore endeavoured to quantify potential reductions in diabetes and disease costs that could result from reducing synthetic chemical diabetogenic exposures in the elderly in Europe. METHODS: We leveraged the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study ( approximately 1000 participants), which has measured exposure to phthalates; dichlorodiphenyltrichloroethylene; polychlorinated biphenyls (PCBs) and perfluoroalkyl substances to examine their independent contribution to diabetes. We estimated risk reductions assuming identical 25% reductions across levels of 4 selected compounds (PCB 153, monoethylphthalate, dichlorodiphenyldichloroethylene and perfluorononanoic acid), and diabetes costs saved in European men and women if diabetogenic exposures are limited. RESULTS: Reduction of chemical exposures was associated with a 13% (95% CI 2% to 22%) reduction in prevalent diabetes, compared with 40% resulting from an identical (25%) reduction in body mass index (BMI) in cross-sectional analyses. Extrapolating to Europe, 152 481 cases of diabetes in Europe and euro4.51 billion/year in associated costs could be prevented, compared with 469 172 cases prevented by reducing BMI. CONCLUSIONS: These findings support regulatory and individual efforts to reduce chemical exposures to reduce the burden and costs of diabetes.

Importance: The increasing use of cesarean delivery is an emerging global health issue. Prior estimates of China's cesarean rate have been based on surveys with limited geographic coverage. Objective: To provide updated information about cesarean rates and geographic variation in cesarean use in China. Design, Setting, and Data Sources: Descriptive study, covering every county (n = 2865) in mainland China's 31 provinces, using county-level aggregated information on the number of live births, cesarean deliveries, maternal deaths, and perinatal deaths, collected by the Office for National Maternal & Child Health Statistics of China, from 2008 through 2014. Exposures: Live births. Main Outcomes and Measures: Annual rate of cesarean deliveries. Results: Over the study period, there were 100873051 live births, of which 32947229 (32.7%) were by cesarean delivery. In 2008, there were 13160634 live births, of which 3788029 (28.8%) were by cesarean delivery and in 2014 there were 15123276 live births, of which 5280124 (34.9%) were by cesarean delivery. Rates varied markedly by province, from 4.0% to 62.5% in 2014. Despite the overall increase, by 2014 rates of cesarean delieries in 14 of the nation's 17 "super cities" had declined by 4.1 to 17.5 percentage points from their earlier peak values (median, 11.4; interquartile range, 6.3-15.4). In 4 super cities with the largest decreases, there was no increase in maternal or perinatal mortality. Conclusions and Relevance: Between 2008 and 2014, the overall annual rate of cesarean deliveries increased in China, reaching 34.9%. There was major geographic variation in rates and trends over time, with rates declining in some of the largest urban areas.

Several developing countries have limited or no information about exposures near anthropogenic mercury sources and no studies have quantified costs of mercury pollution or economic benefits to mercury pollution prevention in these countries. In this study, we present data on mercury concentrations in human hair from subpopulations in developing countries most likely to benefit from the implementation of the Minamata Convention on Mercury. These data are then used to estimate economic costs of mercury exposure in these communities. Hair samples were collected from sites located in 15 countries. We used a linear dose-response relationship that previously identified a 0.18 IQ point decrement per part per million (ppm) increase in hair mercury, and modeled a base case scenario assuming a reference level of 1 ppm, and a second scenario assuming no reference level. We then estimated the corresponding increases in intellectual disability and lost Disability-Adjusted Life Years (DALY). A total of 236 participants provided hair samples for analysis, with an estimated population at risk of mercury exposure near the 15 sites of 11,302,582. Average mercury levels were in the range of 0.48 ppm-4.60 ppm, and 61% of all participants had hair mercury concentrations greater than 1 ppm, the level that approximately corresponds to the USA EPA reference dose. An additional 1310 cases of intellectual disability attributable to mercury exposure were identified annually (4110 assuming no reference level), resulting in 16,501 lost DALYs (51,809 assuming no reference level). A total of $77.4 million in lost economic productivity was estimated assuming a 1 ppm reference level and $130 million if no reference level was used. We conclude that significant mercury exposures occur in developing and transition country communities near sources named in the Minamata Convention, and our estimates suggest that a large economic burden could be avoided by timely implementation of measures to prevent mercury exposures.

BACKGROUND: Preterm birth (PTB) rates (11.4% in 2013) in the United States (US) remain high and are a substantial cause of morbidity. Studies of prenatal exposure have associated particulate matter <2.5microns in diameter (PM2.5) and other ambient air pollutants with adverse birth outcomes, yet, to our knowledge, burden and costs of PM 2.5-attributable PTB have not been estimated in the US. OBJECTIVES: To estimate burden of PTB in the US and economic costs attributable to PM2.5 exposure in 2010. METHODS: Annual deciles of PM2.5 were obtained from US EPA. We converted PTB odds ratio (OR), identified in a previous meta-analysis (1.15 per 10microg/m3 for our base case, 1.07-1.16 for low- and high-end scenarios) to relative risk (RRs), to obtain an estimate that better represents the true relative risk. A reference level (RL) of 8.8microg/m3 was applied. We then used the RR estimates and county-level PTB prevalence to quantify PM2.5 attributable PTB. Direct medical costs were obtained from the 2007 Institute of Medicine report, and lost economic productivity (LEP) was estimated using a meta-analysis of PTB-associated IQ loss, and well-established relationships of IQ loss with LEP. All costs were calculated using 2010 dollars. RESULTS: An estimated 3.32% of PTBs nationally (corresponding to15,808 PTBs) in 2010 could be attributed to PM2.5 (PM2.5>8.8 microg/m3). Attributable PTBs cost were estimated at $4.33 billion (SA: $2.06-8.22B), of which $760 million were spent for medical care (SA: $362M-1.44B). The estimated PM2.5-attributable fraction (AF) of PTB was highest in urban counties, with highest AFs in the Ohio valley and Southern US. CONCLUSIONS: PM2.5 may contribute substantially to burden and costs of PTB in the US, and considerable health and economic benefits could be achieved through environmental regulatory interventions that reduce PM2.5 exposure in pregnancy.

BACKGROUND: Endocrine-disrupting chemicals (EDCs) contribute to disease and dysfunction and incur high associated costs (>1% of the gross domestic product [GDP] in the European Union). Exposure to EDCs varies widely between the USA and Europe because of differences in regulations and, therefore, we aimed to quantify disease burdens and related economic costs to allow comparison. METHODS: We used existing models for assessing epidemiological and toxicological studies to reach consensus on probabilities of causation for 15 exposure-response relations between substances and disorders. We used Monte Carlo methods to produce realistic probability ranges for costs across the exposure-response relation, taking into account uncertainties. Estimates were made based on population and costs in the USA in 2010. Costs for the European Union were converted to US$ (euro1=$1.33). FINDINGS: The disease costs of EDCs were much higher in the USA than in Europe ($340 billion [2.33% of GDP] vs $217 billion [1.28%]). The difference was driven mainly by intelligence quotient (IQ) points loss and intellectual disability due to polybrominated diphenyl ethers (11 million IQ points lost and 43 000 cases costing $266 billion in the USA vs 873 000 IQ points lost and 3290 cases costing $12.6 billion in the European Union). Accounting for probability of causation, in the European Union, organophosphate pesticides were the largest contributor to costs associated with EDC exposure ($121 billion), whereas in the USA costs due to pesticides were much lower ($42 billion). INTERPRETATION: EDC exposure in the USA contributes to disease and dysfunction, with annual costs taking up more than 2% of the GDP. Differences from the European Union suggest the need for improved screening for chemical disruption to endocrine systems and proactive prevention. FUNDING: Endocrine Society, Ralph S French Charitable Foundation, and Broad Reach Foundation.

Evidence increasingly confirms that synthetic chemicals disrupt the endocrine system and contribute to disease and disability across the lifespan. Despite a United Nations Environment Programme/WHO report affirmed by over 100 countries at the Fourth International Conference on Chemicals Management, 'manufactured doubt' continues to be cast as a cloud over rigorous, peer-reviewed and independently funded scientific data. This study describes the sources of doubt and their social costs, and suggested courses of action by policymakers to prevent disease and disability. The problem is largely based on the available data, which are all too limited. Rigorous testing programmes should not simply focus on oestrogen, androgen and thyroid. Tests should have proper statistical power. 'Good laboratory practice' (GLP) hardly represents a proper or even gold standard for laboratory studies of endocrine disruption. Studies should be evaluated with regard to the contamination of negative controls, responsiveness to positive controls and dissection techniques. Flaws in many GLP studies have been identified, yet regulatory agencies rely on these flawed studies. Peer-reviewed and unbiased research, rather than 'sound science', should be used to evaluate endocrine-disrupting chemicals.