Opportunities for evaluating chemical exposures and child health in the United States: the Environmental influences on Child Health Outcomes (ECHO) Program

The Environmental Influences on Child Health Outcomes (ECHO) Program will evaluate environmental factors affecting children’s health (perinatal, neurodevelopmental, obesity, respiratory, and positive health outcomes) by pooling cohorts composed of >50,000 children in the largest US study of its kind. Our objective was to identify opportunities for studying chemicals and child health using existing or future ECHO chemical exposure data. We described chemical-related information collected by ECHO cohorts and reviewed ECHO-relevant literature on exposure routes, sources, and environmental and human monitoring. Fifty-six ECHO cohorts have existing or planned chemical biomonitoring data for mothers or children. Environmental phenols/parabens, phthalates, metals/metalloids, and tobacco biomarkers are each being measured by ≥15 cohorts, predominantly during pregnancy and childhood, indicating ample opportunities to study child health outcomes. Cohorts are collecting questionnaire data on multiple exposure sources and conducting environmental monitoring including air, dust, and water sample collection that could be used for exposure assessment studies. To supplement existing chemical data, we recommend biomonitoring of emerging chemicals, nontargeted analysis to identify novel chemicals, and expanded measurement of chemicals in alternative biological matrices and dust samples. ECHO’s rich data and samples represent an unprecedented opportunity to accelerate environmental chemical research to improve the health of US children

Birth Outcomes in Relation to Prenatal Exposure to Per- and Polyfluoroalkyl Substances and Stress in the Environmental Influences on Child Health Outcomes (ECHO) Program

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are persistent and ubiquitous chemicals associated with risk of adverse birth outcomes. Results of previous studies have been inconsistent. Associations between PFAS and birth outcomes may be affected by psychosocial stress. OBJECTIVES: We estimated risk of adverse birth outcomes in relation to prenatal PFAS concentrations and evaluate whether maternal stress modifies those relationships. METHODS: We included 3,339 participants from 11 prospective prenatal cohorts in the Environmental influences on the Child Health Outcomes (ECHO) program to estimate the associations of five PFAS and birth outcomes. We stratified by perceived stress scale scores to examine effect modification and used Bayesian Weighted Sums to estimate mixtures of PFAS. RESULTS: We observed reduced birth size with increased concentrations of all PFAS. For a 1-unit higher log-normalized exposure to perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA), and perfluorohexane sulfonic acid (PFHxS), we observed lower birthweight-for-gestational-age z-scores of formula presented [95% confidence interval (CI): formula presented ], formula presented (95% CI: formula presented ), formula presented (95% CI: formula presented ), formula presented (95% CI: formula presented , 0.06), and formula presented (95% CI: formula presented ), respectively. We observed a lower odds ratio (OR) for large-for-gestational-age: formula presented (95% CI: 0.38, 0.83), formula presented (95% CI: 0.35, 0.77). For a 1-unit increase in log-normalized concentration of summed PFAS, we observed a lower birthweight-for-gestational-age z-score [formula presented ; 95% highest posterior density (HPD): formula presented ] and decreased odds of large-for-gestational-age (formula presented ; 95% HPD: 0.29, 0.82). Perfluorodecanoic acid (PFDA) explained the highest percentage (40%) of the summed effect in both models. Associations were not modified by maternal perceived stress. DISCUSSION: Our large, multi-cohort study of PFAS and adverse birth outcomes found a negative association between prenatal PFAS and birthweight-for-gestational-age, and the associations were not different in groups with high vs. low perceived stress. This study can help inform policy to reduce exposures in the environment and humans. https://doi.org/10.1289/EHP10723

Dose Estimation for a Study of Nuclear Workers in France, the United Kingdom and the United States of America Methods for the International Nuclear Workers Study (INWORKS)

International audienceIn the framework of the International Nuclear Workers Study conducted in France, the UK and the U.S. (INWORKS), updated and expanded methods were developed to convert recorded doses of ionizing radiation to estimates of organ doses or individual personal dose equivalent [Hp(10)] for a total number of 308,297 workers, including 40,035 women. This approach accounts for differences in dosimeter response to predominant workplace energy and geometry of exposure and for the recently published ICRP report on dose coefficients for men and women separately. The overall mean annual individual personal dose equivalent, including zero doses, is 1.73 mSv [median = 0.42; interquartile range (IQR) 0.07, 1.59]. Associated individual organ doses were estimated. INWORKS includes workers who had potential for exposure to neutrons. Therefore, we analyzed neutron dosimetry data to identify workers potentially exposed to neutrons. We created a time-varying indicator for each worker, classifying them according to whether they had a positive recorded neutron dose and if so, whether their neutron dose ever exceeded 10% of their total external penetrating radiation dose. The number of workers flagged as being exposed to neutrons was 13% for the full cohort, with 15% of the cohort in France, 12% of the cohort in the UK and 14% in the U.S. We also used available information on in vivo and bioassay monitoring to identify workers with known depositions or suspected internal contaminations. As a result of this work, information is now available that will allow various types of sensitivity analyses. © 2015 by Radiation Research Society

Risk of cancer from occupational exposure to ionising radiation Retrospective cohort study of workers in France, the United Kingdom, and the United States (INWORKS)

International audienceStudy question Is protracted exposure to low doses of ionising radiation associated with an increased risk of solid cancer? Methods In this cohort study, 308 297 workers in the nuclear industry from France, the United Kingdom, and the United States with detailed monitoring data for external exposure to ionising radiation were linked to death registries. Excess relative rate per Gy of radiation dose for mortality from cancer was estimated. Follow-up encompassed 8.2 million person years. Of 66 632 known deaths by the end of follow-up, 17 957 were due to solid cancers. Study answer and limitations Results suggest a linear increase in the rate of cancer with increasing radiation exposure. The average cumulative colon dose estimated among exposed workers was 20.9 mGy (median 4.1 mGy). The estimated rate of mortality from all cancers excluding leukaemia increased with cumulative dose by 48% per Gy (90% confidence interval 20% to 79%), lagged by 10 years. Similar associations were seen for mortality from all solid cancers (47% (18% to 79%)), and within each country. The estimated association over the dose range of 0-100 mGy was similar in magnitude to that obtained over the entire dose range but less precise. Smoking and occupational asbestos exposure are potential confounders; however, exclusion of deaths from lung cancer and pleural cancer did not affect the estimated association. Despite substantial efforts to characterise the performance of the radiation dosimeters used, the possibility of measurement error remains. What this study adds The study provides a direct estimate of the association between protracted low dose exposure to ionising radiation and solid cancer mortality. Although high dose rate exposures are thought to be more dangerous than low dose rate exposures, the risk per unit of radiation dose for cancer among radiation workers was similar to estimates derived from studies of Japanese atomic bomb survivors. Quantifying the cancer risks associated with protracted radiation exposures can help strengthen the foundation for radiation protection standards. Funding, competing interests, data sharing Support from the US Centers for Disease Control and Prevention; Ministry of Health, Labour and Welfare of Japan; Institut de Radioprotection et de Sûreté Nucléaire; AREVA; Electricité de France; US National Institute for Occupational Safety and Health; US Department of Energy; and Public Health England. Data are maintained and kept at the International Agency for Research on Cancer. © BMJ Publishing Group Ltd 2015

The international nuclear workers study (INWORKS): A collaborative epidemiological study to improve knowledge about health effects of protracted low-dose exposure

International audienceINWORKS is a multinational cohort study, gathering 308 297 workers in the nuclear industry in France, the United Kingdom and the United States of America, with detailed individual monitoring data for external exposure to ionising radiation. Over a mean duration of follow-up of 27 y, the number of observed deaths was 66 632, including 17 957 deaths due to solid cancers, 1791 deaths due to haematological cancers and 27 848 deaths due to cardiovascular diseases. Mean individual cumulative external dose over the period 1945-2005 was 25 mSv. Analyses demonstrated a significant association between red bone marrow dose and the risk of leukaemia (excluding chronic lymphocytic leukaemia) and between colon dose and the risk of solid cancers. INWORKS assembled some of the strongest evidence to strengthen the scientific basis for the protection of adults from low dose, low-dose rate, exposures to ionising radiation. © The Author 2016

Dose Estimation for a Study of Nuclear Workers in France, the United Kingdom and the United States of America Methods for the International Nuclear Workers Study (INWORKS)

International audienceIn the framework of the International Nuclear Workers Study conducted in France, the UK and the U.S. (INWORKS), updated and expanded methods were developed to convert recorded doses of ionizing radiation to estimates of organ doses or individual personal dose equivalent [Hp(10)] for a total number of 308,297 workers, including 40,035 women. This approach accounts for differences in dosimeter response to predominant workplace energy and geometry of exposure and for the recently published ICRP report on dose coefficients for men and women separately. The overall mean annual individual personal dose equivalent, including zero doses, is 1.73 mSv [median = 0.42; interquartile range (IQR) 0.07, 1.59]. Associated individual organ doses were estimated. INWORKS includes workers who had potential for exposure to neutrons. Therefore, we analyzed neutron dosimetry data to identify workers potentially exposed to neutrons. We created a time-varying indicator for each worker, classifying them according to whether they had a positive recorded neutron dose and if so, whether their neutron dose ever exceeded 10% of their total external penetrating radiation dose. The number of workers flagged as being exposed to neutrons was 13% for the full cohort, with 15% of the cohort in France, 12% of the cohort in the UK and 14% in the U.S. We also used available information on in vivo and bioassay monitoring to identify workers with known depositions or suspected internal contaminations. As a result of this work, information is now available that will allow various types of sensitivity analyses. © 2015 by Radiation Research Society