Faculty Bibliography

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.

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.

OBJECTIVE: To explore the association of sleep duration and awakening frequency with cognitive outcomes in young children. METHODS: Mothers of 2,800 children from the Generation R cohort reported sleep duration and awakenings at children's age 24 months. At age 6 years, validated Dutch measures were used to assess children's nonverbal intelligence and language comprehension. RESULTS: We found a nonlinear association of total sleep time at 24 months with nonverbal intelligence (p = 0.03) and language comprehension (p = 0.04) at 6 years. Toddlers sleeping within the recommended 11-14 hr had more favorable cognitive development compared with both extremes. Frequent awakenings were negatively associated with nonverbal intelligence, but not with verbal comprehension. CONCLUSION: Sleep duration in toddlerhood has an inverted-U-shaped relation with childhood cognitive measures. Frequent awakenings are associated with lower nonverbal intelligence. Given the marked decline in sleep duration and awakenings in toddlerhood, developmental changes of sleep patterns might be important for cognitive development.

OBJECTIVE:We examined the longitudinal associations of age at achieving gross motor milestones and children's development in a US cohort of singletons and twins. METHODS:In the Upstate KIDS study, a population-based study of children born between 2008 and 2010, information on age at achievement of motor milestones and developmental skills was available in 599 children (314 singletons, 259 twins, and 26 triplets). Mothers reported their children's major motor milestones at ∼4, 8, 12, 18, and 24 months. At age 4 years, children's development was clinically assessed by using the Battelle Developmental Inventory, Second Edition (BDI-2). Primary analyses by using multivariate linear regressions were conducted in singletons. We also examined the associations in twins. RESULTS:Later achievement of standing with assistance predicted lower BDI-2 scores in singletons in adjusted models (B per SD of age at achievement, -21.9 [95% confidence interval (CI), -41.5 to -2.2]). Post hoc analysis on age of standing with assistance showed that associations were driven by differences in adaptive skills (B = -5.3 [95% CI, -9.0 to -1.6]) and cognitive skills (B = -5.9 [95% CI, -11.5 to -0.4]). Analyses restricted to twins suggested no association between the age at achievement of milestones and total BDI-2 score after adjustment for gestational age and birth weight. CONCLUSIONS:This study provides evidence that the age of achieving motor milestones may be an important basis for various aspects of later child development. In twins, key predictors of later development (eg, perinatal factors) overshadow the predictive role of milestones in infancy.

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.

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.