Association between Residential Proximity to Viticultural Areas and Childhood Acute Leukemia Risk in Mainland France: GEOCAP Case-Control Study, 2006-2013.

BACKGROUND: Pesticide exposures are suspected of being a risk factor for several childhood cancers, particularly acute leukemia (AL). Most of the evidence is based on self-reported parental domestic use of pesticides, but some studies have also addressed associations with agricultural use of pesticides near the place of residence. OBJECTIVES: The objective of the study was to evaluate the risk of AL in children living close to vines, a crop subject to intensive pesticide use. METHODS: Data were drawn from the national registry-based GEOCAP study. We included all of the AL cases under the age of 15 years diagnosed in 2006-2013 (n=3,711) and 40,196 contemporary controls representative of the childhood population in France. The proximity of the vines (probability of presence within 200, 500, and 1,000m) and the viticulture density (area devoted to vines within 1,000m) were evaluated around the geocoded addresses in a geographic information system combining three national land use maps. Logistic regression models were used to estimate odds ratios (ORs) for all AL and for the lymphoblastic (ALL) and myeloid (AML) subtypes. Heterogeneity between regions was studied by stratified analyses. Sensitivity analyses were carried out to take into account, in particular, geocoding uncertainty, density of other crops and potential demographic and environmental confounders. RESULTS: In all, about 10% of the controls lived within 1km of vines. While no evidence of association between proximity to vines and AL was found, viticulture density was positively associated with ALL [OR=1.05 (1.00-1.09) for a 10% increase in density], with a statistically significant heterogeneity across regions. No association with AML was observed. The results remained stable in all the sensitivity analyses. CONCLUSION: We evidenced a slight increase in the risk of ALL in children living in areas with high viticulture density. This finding supports the hypothesis that environmental exposure to pesticides may be associated with childhood ALL. https://doi.org/10.1289/EHP12634.

Increasing incidence and spatial hotspots of hospitalized endometriosis in France from 2011 to 2017.

Endometriosis is a female hormone-dependent disease, possibly related to endocrine disruptor exposure. We aimed to monitor this disease nationwide in France and analyze spatial trends at a fine scale to explore possible environmental contributing risk factors. We conducted a retrospective national descriptive study from 2011 to 2017 in females aged 10 years old and over, using comprehensive hospital discharge data. Cases were identified using ICD-10 N80 codes and were localized at their municipality of residence. We defined incident cases as the first hospital stay of patients, without a stay in at least the previous 5 years. We performed statistical analyses according to age and type of endometriosis, and we modeled the temporal, spatial and spatiotemporal trends. We identified 207,462 incident cases of all-type hospitalized endometriosis (83,112 for non-adenomyosis cases). The crude incidence rate for the study period was 9.85/10,000 person-years (3.95/10,000 for non-adenomyosis cases). From 2011 to 2017, the risk of all-type endometriosis increased by 8.5% (95% CI: 3.9; 13.4) (by 3.6% (95% CI: 0.6; 6.8) for non-adenomyosis cases). The risk was geographically heterogeneous, with 20 high-risk hotspots, showing similar results for non-adenomyosis cases. Shifting practice patterns, improved awareness and healthcare disparities interlinked with environmental risk factors could explain these trends.

Dengue serosurvey after a 2-month long outbreak in Nîmes, France, 2015: was there more than met the eye?

BackgroundClusters of dengue cases have recently become more frequent in areas of southern France colonised by the vector mosquito Aedes albopictus. In July 2015, a 2-month outbreak of dengue virus serotype 1 (DENV-1) was reported in Nîmes. Aim: We conducted a serosurvey in the affected area at the end of the vector activity period to determine the true extent of dengue transmission. Methods: We collected capillary blood from consenting household members, and information on their medical and travel histories, and exposure to mosquito bites. Recent infections were identified using IgM and IgG anti-DENV ELISA, followed, when positive, by plaque reduction neutralisation tests on serum against DENV 1-4 and West Nile virus. The prevalence estimator was calibrated on reference demographic data. We quantified the spatial clustering of dengue cases within the affected community and inferred the transmission tree. Results: The study participation rate was 39% (564/1,431). Three of 564 participants tested positive for DENV-1 infection (after marginal calibration, 0.41%; 95% confidence interval: 0.00-0.84). The spatial analysis showed that cases were clustered at the household level. Most participants perceived the presence of mosquitos as abundant (83%) and reported frequent mosquito bites (57%). We incidentally identified six past West Nile virus infections (0.9%; 95% CI: 0.2-1.6). Conclusion: This serosurvey confirms the potential for arboviral diseases to cause outbreaks - albeit limited for now - in France and Europe.

Urinary levels of pyrethroid pesticides and determinants in pregnant French women from the Elfe cohort.

Pyrethroids are insecticides which are widely used for agricultural and domestic purposes. The general population can be exposed to them. Given the suspected effects of pesticides on the development of the foetus, exposure to pyrethroids during pregnancy is a major public health concern. The objective of this paper is to describe the urinary levels of the following five pyrethroid metabolites and their associated determinants among pregnant French women in 2011 enrolled in the Elfe cohort (n = 1077): a) 3-phenoxy benzoic (3-PBA), b) 4­fluoro­3­phenoxy benzoic acid (4-F-3-PBA), c) Cis­3­(2,2dibromovinyl)­2,2­dimethyl cyclopropane-carboxylic acid (Cis-DBCA); d) Cis­3­(2,2dichlorovinyl)­2,2­dimethyl cyclopropane-carboxylic acid (Cis-DCCA) and e) Trans-3­(2,2dichlorovinyl)­2,2­dimethyl cyclopropane-carboxylic acid (Trans-DCCA). The distribution levels were estimated for each pyrethroid metabolite. Multivariable analyses helped determine the predictors of these levels. All metabolites except 4-F-3-PBA were detected in all the urine samples. The mean urinary concentration of the sum of the metabolites (3-PBA, Cis-DBCA, Cis-DCCA, Trans-DCCA) was 1.18 µg/L, with the highest concentrations observed for 3-PBA. A comparison of these levels with other studies showed that pregnant French women tend to be more exposed to pyrethroids than their American counterparts, less exposed than Chinese and Caribbean mothers, and have similar exposure to Japanese mothers. In our study, urinary levels of pyrethroid metabolites were positively related to smoking during pregnancy, consuming fish and alcohol, domestic pesticide use and living in the vicinity of crops during pregnancy. These findings highlight the importance of non-dietary pathways when evaluating exposure to pyrethroids.

Epidemiology of Childhood Hyperthyroidism in France: A Nationwide Population-Based Study.

Context: Hyperthyroidism affects all age groups, but epidemiological data for children are scarce. Objective: To perform a nationwide epidemiological survey of hyperthyroidism in children and adolescents. Design: A cross-sectional descriptive study. Setting: Identification of entries corresponding to reimbursements for antithyroid drugs in the French national insurance database. Participants: All cases of childhood hyperthyroidism (6 months to 17 years of age) in 2015. Main Outcome Measures: National incidence rate estimated with a nonlinear Poisson model and spatial distribution of cases. Results: A total of 670 cases of childhood hyperthyroidism were identified. Twenty patients (3%) had associated autoimmune or genetic disease, with type 1 diabetes and Down syndrome the most frequent. The annual incidence for 2015 was 4.58/100,000 person-years (95% CI 3.00 to 6.99/100,000). Incidence increased with age, in both sexes. This increase accelerated after the age of 8 in girls and 10 in boys and was stronger in girls. About 10% of patients were affected before the age of 5 years (sex ratio 1.43). There was an interaction between age and sex, the effect of being female increasing with age: girls were 3.2 times more likely to be affected than boys in the 10 to 14 years age group and 5.7 times more likely to be affected in the 15 to 17 years age group. No conclusions about spatial pattern emerged. Conclusion: These findings shed light on the incidence of hyperthyroidism and the impact of sex on this incidence during childhood and adolescence. The observed incidence was higher than expected from the results published for earlier studies in Northern European countries.

Prenatal exposure to lead in France: Cord-blood levels and associated factors: Results from the perinatal component of the French Longitudinal Study since Childhood (Elfe).

BACKGROUND: As a result of the ban on lead in gasoline on 2nd January 2000, the French population's exposure to lead has decreased in recent years. However, because of the acknowledged harmful cognitive effects of lead even at low levels, lead exposure remains a major public health issue. In France, few biomonitoring data are available for exposure to lead in pregnant women and newborn. The purpose of the perinatal component of the French human biomonitoring (HBM) program was to describe levels of various biomarkers of exposure to several environmental pollutants, including lead, among mother-baby pairs. In this paper, we aimed to describe the distribution of cord blood lead levels (CBLL) in French mother-baby pairs, and to estimate the contribution of the main lead exposure risk factors to these levels. METHOD: A total of 1968 mother-baby pairs selected from the participants of the perinatal component of the French HBM program were included in the study on lead. Lead levels were analyzed in cord blood collected at child delivery by inductively coupled plasma-mass spectrometry (ICP-MS). The data collected included biological sample, socio-demographic characteristics, environmental and occupational exposure, and information on dietary factors. RESULTS: CBLL were quantified for 99.5% of the sample. The CBLL geometric mean was 8.30 µg/l (95% CI [7.94-8.68]) with a 95th percentile of 24.3 µg/l (95% CI [20.7-27.1]). Factors significantly associated with CBLL were tap water consumption, alcohol consumption, shellfish consumption, vegetable consumption, bread consumption, smoking, and the mother being born in countries where lead is often used. CONCLUSION: This study provides the first reference value for CBLL in a random sample of mother-baby pairs not particularly exposed to high levels of lead (24.3 µg/l). A substantial decrease in CBLL over time was observed, which confirms the decrease of exposure to lead among the general population. CBLL observed in this French study were in the range of those found in recent surveys conducted in other countries.

Biomarkers of exposure to environmental contaminants in French pregnant women from the Elfe cohort in 2011.

BACKGROUND: As part of the perinatal component of the French Human Biomonitoring (HBM) program, biomarkers levels of various chemicals have been described among pregnant women having given birth in continental France in 2011 and who have been enrolled in the Elfe cohort (French Longitudinal Study since Childhood). This paper describes the design of the study and provides main descriptive results regarding exposure biomarkers levels. METHODS: Exposure biomarkers were measured in biological samples collected at delivery from pregnant women randomly selected among the participants in the clinical and biological component of the Elfe cohort (n=4145). The geometric mean and percentiles of the levels distribution were estimated for each biomarker. The sampling design was taken into account in order to obtain estimates representative of the French pregnant women in 2011. RESULTS: Results provide a nation-wide representative description of biomarker levels for important environmental contaminants among pregnant women who gave birth in France in 2011. Bisphenol A (BPA), and some metabolites of phthalates, pesticides (mainly pyrethroids), dioxins, furans, polychlorobiphenyls (PCBs), brominated flame retardants (BFRs), perfluorinated compounds (PFCs) and metals (except uranium) were quantified in almost 100% of the pregnant women. Some compounds showed a downward trend compared to previous studies (lead, mercury), but others did not (pyrethroids) and should be further monitored. CONCLUSION AND PERSPECTIVES: The present results show that French pregnant women are exposed to a wide variety of pollutants, including some that have been banned or restricted in France.

The mortality impacts of fine particles in France.

INTRODUCTION: Worldwide, air pollution has become a main environmental cause of premature mortality. This burden is largely due to fine particles. Recent cohort studies have confirmed the health risks associated with chronic exposure to PM2.5 for European and French populations. We assessed the mortality impact of PM2.5 in continental France using these new results. METHODS: Based on a meta-analysis of French and European cohorts, we computed a shrunken estimate of PM2.5-mortality relationship for the French population (RR 1.15 [1.05:1.25] for a 10µg/m(3) increase in PM2.5). This RR was applied to PM2.5 annual concentrations estimated at a fine spatial scale, using a classical health impacts assessment method. The health benefits associated with alternative scenarios of improving air quality were computed for 36,219 French municipalities for 2007-2008. RESULTS: 9% of the total mortality in continental France is attributable to anthropogenic PM2.5. This represents >48,000 deaths per year, and 950,000years of life lost per year, more than half occurring in urban areas larger than 100,000 inhabitants. If none of the municipalities exceeded the World Health Organization guideline value for PM2.5 (10µg/m(3)), the total mortality could be decreased by 3%, corresponding to 400,000years of life saved per year. CONCLUSION: Results were consistent with previous estimates of the long-term mortality impacts of fine particles in France. These findings show that further actions to improve air quality in France would substantially improve health.

How to estimate exposure when studying the temperature-mortality relationship? A case study of the Paris area.

Time series studies assessing the effect of temperature on mortality generally use temperatures measured by a single weather station. In the Paris region, there is a substantial measurement network, and a variety of exposure indicators created from multiple stations can be tested. The aim of this study is to test the influence of exposure indicators on the temperature-mortality relationship in the Paris region. The relationship between temperature and non-accidental mortality was assessed based on a time series analysis using Poisson regression and a generalised additive model. Twenty-five stations in Paris and its three neighbouring departments were used to create four exposure indicators. These indicators were (1) the temperature recorded by one reference station, (2) a simple average of the temperatures of all stations, (3) an average weighted on the departmental population and (4) a classification of the stations based on land use and an average weighted on the population in each class. The relative risks and the Akaike criteria were similar for all the exposure indicators. The estimated temperature-mortality relationship therefore did not appear to be significantly affected by the indicator used, regardless of study zone (departments or region) or age group. The increase in temperatures from the 90(th) to the 99(th) percentile of the temperature distribution led to a significant increase in mortality over 75 years (RR = 1.10 [95% CI, 1.07; 1.14]). Conversely, the decrease in temperature between the 10(th) and 1(st) percentile had a significant effect on the mortality under 75 years (RR = 1.04 [95% CI, 1.01; 1.06]). In the Paris area, there is no added value in taking multiple climatic stations into account when estimating exposure in time series studies. Methods to better represent the subtle temperature variations in densely populated areas in epidemiological studies are needed.

Semen quality trends in French regions are consistent with a global change in environmental exposure.

A retrospective study carried out recently in a large sample of men, close to the general population, has reported a significant and strong decline in sperm concentration and morphology in the whole of France between 1989 and 2005. We studied these trends within each region of France. Data were obtained from the Fivnat database. The study sample comprised male partners of sterile women in whom both tubes were absent or blocked. They were located at the assisted reproductive technology center. A Bayesian spatio-temporal model with parametric time trends, adjusted for age, was used to model overall time trends for each region. The results show that sperm concentration decreased in almost all regions of France. Among them, Aquitaine showed the highest decrease and Midi-Pyrénées had the lowest average for the whole period. Regarding total motility, most regions showed a slight increase while Bourgogne showed a steep and significant decrease. While considering sperm morphology, there was a decrease in most of the regions. The decrease in Aquitaine and Midi-Pyrénées was stronger when compared with the overall trend. In conclusion, a decrease in sperm concentration and morphology, already shown at the French metropolitan territory level, was observed in most regions of France. This is consistent with a global change in environmental exposure, according to the endocrine disruptor hypothesis especially. Indeed, ubiquitary exposure to chemicals has been growing in the general population of France since the 1950s, and the results do not appear to support the lifestyle hypothesis. The highest decreases and lowest values are consistently observed in two proximate regions that are both highly agricultural and densely populated.

Risk of cancer in the vicinity of municipal solid waste incinerators: importance of using a flexible modelling strategy.

BACKGROUND: We conducted an ecological study in four French administrative departments and highlighted an excess risk in cancer morbidity for residents around municipal solid waste incinerators. The aim of this paper is to show how important are advanced tools and statistical techniques to better assess weak associations between the risk of cancer and past environmental exposures. METHODS: The steps to evaluate the association between the risk of cancer and the exposure to incinerators, from the assessment of exposure to the definition of the confounding variables and the statistical analysis carried out are detailed and discussed. Dispersion modelling was used to assess exposure to sixteen incinerators. A geographical information system was developed to define an index of exposure at the IRIS level that is the geographical unit we considered. Population density, rural/urban status, socio-economic deprivation, exposure to air pollution from traffic and from other industries were considered as potential confounding factors and defined at the IRIS level. Generalized additive models and Bayesian hierarchical models were used to estimate the association between the risk of cancer and the index of exposure to incinerators accounting for the confounding factors. RESULTS: Modelling to assess the exposure to municipal solid waste incinerators allowed accounting for factors known to influence the exposure (meteorological data, point source characteristics, topography). The statistical models defined allowed modelling extra-Poisson variability and also non-linear relationships between the risk of cancer and the exposure to incinerators and the confounders. CONCLUSION: In most epidemiological studies distance is still used as a proxy for exposure. This can lead to significant exposure misclassification. Additionally, in geographical correlation studies the non-linear relationships are usually not accounted for in the statistical analysis. In studies of weak associations it is important to use advanced methods to better assess dose-response relationships with disease risk.

Risk for non Hodgkin's lymphoma in the vicinity of French municipal solid waste incinerators.

BACKGROUND: Dioxin emissions from municipal solid waste incinerators are one of the major sources of dioxins and therefore are an exposure source of public concern. There is growing epidemiologic evidence of an increased risk for non-Hodgkin's lymphoma (NHL) in the vicinity of some municipal solid waste incinerators with high dioxin emission levels. The purpose of this study was to examine this association on a larger population scale. METHODS: The study area consisted of four French administrative departments, comprising a total of 2270 block groups. NHL cases that had been diagnosed during the period 1990-1999, and were aged 15 years and over, were considered. Each case was assigned a block group by residential address geocoding. Atmospheric Dispersion Model System software was used to estimate immissions in the surroundings of 13 incinerators which operated in the study area. Then, cumulative ground-level dioxin concentrations were calculated for each block group. Poisson multiple regression models, incorporating penalized regression splines to control for covariates and dealing with Poisson overdispersion, were used. Five confounding factors were considered: population density, urbanisation, socio-economic level, airborne traffic pollution, and industrial pollution. RESULTS: A total of 3974 NHL incident cases was observed (2147 among males, and 1827 among females) during the 1990-1999 time period. A statistically significant relationship was found at the block group level between risk for NHL and dioxin exposure, with a relative risk (RR) of 1.120 (95% confidence interval [CI] 1.002 - 1.251) for persons living in highly exposed census blocks compared to those living in slightly exposed block groups. Population density appeared positively linked both to risk for NHL and dioxin exposure. Subgroup multivariate analyses per gender yielded a significant RR for females only (RR = 1.178, 95% CI 1.013 - 1.369). CONCLUSION: This study, in line with previous results obtained in the vicinity of the incinerator located in Besançon (France), adds further evidence to the link between NHL incidence and exposure to dioxins emitted by municipal solid waste incinerators. However, the findings of this study cannot be extrapolated to current incinerators, which emit lower amounts of pollutants.