PBPK modeling to support risk assessment of pyrethroid exposure in French pregnant women.

BACKGROUND: Pyrethroids are widely used pesticides and are suspected to affect children's neurodevelopment. The characterization of pyrethroid exposure during critical windows of development, such as fetal development and prenatal life, is essential to ensure a better understanding of pyrethroids potential effects within the concept of Developmental Origins of Health and Disease. OBJECTIVE: The aim of this study was to estimate maternal exposure of French pregnant women from biomonitoring data and simulate maternal and fetal internal concentrations of 3 pyrethroids (permethrin, cypermethrin and deltamethrin) using a multi-substance pregnancy-PBPK (physiologically based pharmacokinetics) model. The estimated maternal exposures were compared to newly proposed toxicological reference values (TRV) children specific also called draft child-specific reference value to assess pyrethroid exposure risk during pregnancy i.e. during the in utero exposure period. METHODS: A pregnancy-PBPK model was developed based on an existing adult pyrethroids model. The maternal exposure to each parent compound of pregnant women of the Elfe (French Longitudinal Study since Childhood) cohort was estimated by reverse dosimetry based on urinary biomonitoring data. To identify permethrin and cypermethrin contribution to their common urinary biomarkers of exposure, an exposure ratio based on biomarkers in hair was tested. Finally, exposure estimates were compared to current and draft child-specific reference values derived from rodent prenatal and postnatal exposure studies. RESULTS: The main contributor to maternal pyrethroid diet intake is cis-permethrin. In blood, total internal concentrations main contributor is deltamethrin. In brain, the major contributors to internal pyrethroid exposure are deltamethrin for fetuses and cis-permethrin for mothers. Risk is identified only for permethrin when referring to the draft child-specific reference value. 2.5% of the population exceeded permethrin draft child-specific reference value. CONCLUSIONS: A new reverse dosimetry approach using PBPK model combined with human biomonitoring data in urine and hair was proposed to estimate Elfe pregnant population exposure to a pyrethroids mixture with common metabolites.

Maternal occupational exposure to carbonaceous nanoscale particles and neurodevelopmental outcomes in early childhood: Analysis of the French Longitudinal Study of Children - Elfe study.

OBJECTIVE: To investigate the association between occupational exposures to carbonaceous unintentionally emitted nanoscale particles (UNPs) during pregnancy and the child's language development and behaviour at two years old. METHODS: Using data from the French Longitudinal Study of Childhood - ELFE, we selected mothers who worked during pregnancy and their children. Exposure to carbonaceous UNPs was assessed by the MatPUF (job-exposure matrix for ultrafine particles). Children's lexical development was analysed using 'the Mac Arthur - Bates communicative development inventories-words and sentences-short form' (MB-CDI) in a multivariate binary logistic regression. Their risk for autism spectrum disorders was studied using 'the Modified-CHecklist for Autism in Toddler' (M-CHAT) according to the recommended thresholds (low risk = 0-2; intermediate risk = 3-6 and high risk = 7-23) in unordered multinomial logistic regression models. RESULTS: Maternal occupational exposure to carbonaceous UNPs was associated with delayed child language development (ORadj: 1.34; 95 % CI: 1.00, 1.80) but not with behavioural disorders (autism spectrum disorders) at two years old. CONCLUSION: This is the first epidemiological study to show a significant association between maternal occupational exposure to carbonaceous nanoscale particles and child language development at 2 years old.

SARS-CoV-2 seroprevalence in French 9-year-old children and their parents after the first lockdown in 2020.

Introduction: Children have been significantly less affected by COVID-19 than adults and presented with milder and less symptomatic forms of the disease. However, there has been suggestion that children older than 10 years and adolescents exhibits features closer to that of young adults. Most studies combine children in different age-groups and lack sufficient numbers to explore in detail age specificities. We report data on a population-based sample of 2,555 children at the pivotal age of 9 years. Methods: In April 2020, the participants in two French nationwide cohorts of children, Elfe and Epipage2, were invited to take part into an online survey about Covid related symptoms and family life during the lockdown. A second questionnaire was sent on May 5. This questionnaire also proposed to the child included in the cohort and to one of his/her parents to take part into a capillary blood collection for Covid serology. Families who agreed to the serological survey were sent kits for dried blood spots self-sampling (DBS) with instructions. Samples were processed with a commercial Elisa test (Euroimmun®, Lübeck, Germany) to detect anti-SARS-CoV-2 antibodies (IgG) directed against the S1 domain of the spike protein of the virus. Results: Children's acceptance rate for the serological survey was around 60%. 2,555 serological results were analyzed. The weighted prevalence of a positive Elisa Spike serology was 2.8% in 9 yr-old children (95% CI: 1.7%-4.0%). Positive serology was found in 8.6% (7.4%-9.7%) of parents who provided blood. There was a significant association (p < 0.001) between serology of the child and parent from the same household with an odds ratio of 13.8 (7.9-24.2). Discussion: We have shown that 9-yr old children had a lower susceptibility to SARS-Cov2 infection than adults with the initial Chinese strain, similar to younger children and estimated that around 3% of them have developed antibodies against SARS-Cov2 in France after the first wave of the Covid-19 epidemics.

Early Life Factors Influencing Children Gut Microbiota at 3.5 Years from Two French Birth Cohorts.

Early life gut microbiota-influencing factors may play an important role in programming individuals long-term health and substantial efforts have been devoted into studying the development of the gut microbiota in relation to early life events. This study aimed to examine in a single study, the persistence of associations between 20 factors occurring in the early life and the gut microbiota at 3.5 years of 798 children from two French nationwide birth cohorts, EPIPAGE 2 (very preterm children) and ELFE (late preterm and full-term children). Gut microbiota profiling was assessed using 16S rRNA gene sequencing-based method. Upon thorough adjustment of confounding factors, we demonstrated that gestational age was one of the factors most associated with gut microbiota differences with a noticeable imprint of prematurity at 3.5 years of age. Children born by cesarean section harbored lower richness and diversity and a different overall gut microbiota composition independently of preterm status. Children who had ever received human milk were associated with a Prevotella-driven enterotype (P_type) compared to those who had never received human milk. Living with a sibling was associated with higher diversity. Children with siblings and those attending daycare centers were associated with a P_type enterotype. Maternal factors including the country of birth and preconception maternal body mass index were associated with some microbiota characteristics: children born to overweight or obese mothers showed increased gut microbiota richness. This study reveals that multiple exposures operating from early life imprint the gut microbiota at 3.5 years that is a pivotal age when the gut microbiota acquires many of its adult characteristics.

Maternal occupational exposure to organic solvents and intrauterine growth in the ELFE cohort.

BACKGROUND: In developed countries, about 15% of women are occupationally exposed to solvents. Associations between this maternal occupational exposure and intrauterine fetal growth are inconsistent, but almost no existing study has investigated this relation by solvent family (oxygenated, petroleum, and chlorinated), although they may affect fetal growth differently. OBJECTIVES: To investigate the relations between maternal occupational solvent exposure, by solvent family, and the risk of neonates born small for gestational age (SGA), or with low birthweight, or with small head circumference (HC). METHODS: Among the 18,040 women enrolled in the Elfe rather than included in the Elfe birth cohort, we included 13,026 women who worked during pregnancy (72% of the cohort). Information about maternal occupations and industrial activities during pregnancy was collected by questionnaire at the maternity ward, and completed at 2-month when necessary. Using Matgéné job-exposure matrices, we assessed maternal occupational exposure to solvents. Logistic and multiple linear regressions were used to assess the association between maternal occupational solvent exposure and SGA status, birth weight, and HC. Analyses were conducted for exposure during pregnancy and also stratified by the trimester that pregnancy leave began. RESULTS: We observed a higher risk of SGA newborns among mothers occupationally exposed during pregnancy to petroleum solvents (ORadjusted = 1.26; 95%CI: 1.01 to 1.57). Among women working until the third trimester of pregnancy, we observed a higher risk of SGA newborns to those occupationally exposed to oxygenated solvents (ORadjusted = 1.75; 95%CI: 1.11 to 2.75), a significantly lower birthweight for infants of mothers exposed to petroleum solvents (ßadjusted = -47.37 g; -89.33 to -5.42), and a lower HC among newborns of those occupationally exposed to oxygenated solvents (ßadjusted = -0.28; -0.49 to -0.07) and to chlorinated solvents (ßadjusted = -0.29; -0.53 to -0.05). DISCUSSION: Our results suggest that maternal occupational solvent exposure may influence fetal growth, especially exposure into the third trimester of pregnancy.

Intervention during the Perinatal Period: Synthesis of the Clinical Practice Guidelines from the French National College of Midwives.

These clinical practice guidelines from the French National College of Midwives (CNSF) are intended to define the messages and the preventive interventions to be provided to women and co-parents by the different professionals providing care to women or their children during the perinatal period. These guidelines are divided into 10 sections, corresponding to 4 themes: 1/ the adaptation of maternal behaviors (physical activity, psychoactive agents); 2/ dietary behaviors; 3/ household exposure to toxic substances (household uses, cosmetics); 4/ promotion of child health (breastfeeding, attachment and bonding, screen use, sudden unexplained infant death, and shaken baby syndrome). We suggest a ranking to prioritize the different preventive messages for each period, to take into account professionals' time constraints.

Maternal Ambient Exposure to Atmospheric Pollutants during Pregnancy and Offspring Term Birth Weight in the Nationwide ELFE Cohort.

BACKGROUND: Studies have reported associations between maternal exposure to atmospheric pollution and lower birth weight. However, the evidence is not consistent and uncertainties remain. We used advanced statistical approaches to robustly estimate the association of atmospheric pollutant exposure during specific pregnancy time windows with term birth weight (TBW) in a nationwide study. METHODS: Among 13,334 women from the French Longitudinal Study of Children (ELFE) cohort, exposures to PM2.5, PM10 (particles < 2.5 µm and <10 µm) and NO2 (nitrogen dioxide) were estimated using a fine spatio-temporal exposure model. We used inverse probability scores and doubly robust methods in generalized additive models accounting for spatial autocorrelation to study the association of such exposures with TBW. RESULTS: First trimester exposures were associated with an increased TBW. Second trimester exposures were associated with a decreased TBW by 17.1 g (95% CI, -26.8, -7.3) and by 18.0 g (-26.6, -9.4) for each 5 µg/m3 increase in PM2.5 and PM10, respectively, and by 15.9 g (-27.6, -4.2) for each 10 µg/m3 increase in NO2. Third trimester exposures (truncated at 37 gestational weeks) were associated with a decreased TBW by 48.1 g (-58.1, -38.0) for PM2.5, 38.1 g (-46.7, -29.6) for PM10 and 14.7 g (-25.3, -4.0) for NO2. Effects of pollutants on TBW were larger in rural areas. CONCLUSIONS: Our results support an adverse effect of air pollutant exposure on TBW. We highlighted a larger effect of air pollutants on TBW among women living in rural areas compared to women living in urban areas.

Prenatal exposure to pesticides and risk of preeclampsia among pregnant women: Results from the ELFE cohort.

BACKGROUND: Preeclampsia is a pregnancy-specific syndrome caused by abnormal placentation. Although environmental chemicals, including some pesticides, are suspected of impairing placentation and promoting preeclampsia, its relationship with preeclampsia has been insufficiently explored. OBJECTIVES: We aimed to investigate the relation between non-occupational exposure to pesticides during pregnancy and the risk of preeclampsia. METHODS: The study cohort comprised 195 women with and 17,181 without preeclampsia from the ELFE birth cohort. We used toxicogenomic approaches to select 41 pesticides of interest for their possible influence on preeclampsia. We assessed household pesticide use (self-reported data), environmental exposure to agricultural pesticides (geographic information systems), and dietary exposure (food-frequency questionnaire with data from monitoring pesticide residues in food and water). Dietary exposures to pesticides were grouped into clusters of similar exposures to resolve collinearity issues. For each exposure source, pesticides were mutually adjusted, and odds ratios estimated with logistic regression models. RESULTS: The quantity of prochloraz applied within a kilometer of the women's homes was higher in women with than without preeclampsia (fourth quartile vs. others; adjusted odds ratio [aOR] = 1.54; 95%CI: 1.02, 2.35), especially when preeclampsia was diagnosed before 34 weeks of gestation (aOR = 2.25; 95%CI: 1.01, 5.06). The reverse was observed with nearby cypermethrin application (aOR = 0.59, 95%CI: 0.36, 0.96). In sensitivity analyses, women with preeclampsia receiving antihypertensive treatment had a significantly higher probability of using herbicides at home during pregnancy than women without preeclampsia (aOR = 2.20; 95%CI: 1.23, 3.93). No statistically significant association was found between dietary exposure to pesticide residues and preeclampsia. DISCUSSION: While the most of the associations examined remained statistically non-significant, our results suggest the possible influence on preeclampsia of residential exposures to prochloraz and some herbicides. These estimations are supported by toxicological and mechanistic data.

Hair versus urine for the biomonitoring of pesticide exposure: Results from a pilot cohort study on pregnant women.

BACKGROUND/AIM: The quantitative assessment of human exposure to contaminants such as pesticides is a crucial step in the characterization of exposure-associated risk. For this purpose, biomonitoring is often privileged as it presents the advantage of integrating all the possible sources and routes of exposure and of being representative of the internal dose resulting from exposure. Although biological fluids such as urine and blood have been used to date for this purpose, increasing interest has also been observed over the past decade for hair analysis. The present work aimed at comparing the information obtained from the analysis of urine versus hair regarding exposure to pesticides in a pilot cohort of pregnant women. METHODS: In ninety-three pregnant women included in the pilot of the French cohort ELFE, one urine and one hair sample were collected simultaneously from each subject at the maternity. Samples were analyzed using GC-MS/MS analytical methods allowing for the detection of both parent pesticides and metabolites, and designed to be as similar as possible between urine and hair for reliable inter-matrix comparison. Fifty-two biomarkers of exposure were targeted, including parents and metabolites of organochlorines, organophosphates, pyrethroids, carbamates, phenylpyrazoles and other pesticides. RESULTS: The number of different compounds detected ranged from 16 to 27 (median = 22) in hair, and from 3 to 22 (median = 12) in urine. In hair, 24 compounds were found in > 40% of the individuals, whereas only 12 compounds presented the same frequency of detection in urine. Among the chemicals detected in > 80% of both hair and urine samples, only one (pentachlorophenol) showed a signification correlation between hair and urine concentrations. CONCLUSIONS: The present results highlight the multiple exposure of the pregnant women included in this cohort and suggest that hair provides more comprehensive information on pesticide exposure than urine analysis. This study thus supports the relevance of hair analysis in future epidemiological studies investigating association between exposure and adverse health effects.

Human exposure to PCBs, PBDEs and bisphenols revealed by hair analysis: A comparison between two adult female populations in China and France.

Humans are exposed to various anthropogenic chemicals in daily life, including endocrine-disrupting chemicals (EDCs). However, there are limited data on chronic, low-level exposure to such contaminants among the general population. Here hair analysis was used to investigate the occurrence of four polychlorinated biphenyls (PCBs), seven polybrominated diphenyl ethers (PBDEs) and two bisphenols (BPs) in 204 Chinese women living in the urban areas of Baoding and Dalian and 311 pregnant French women. All the PCBs and PBDEs tested here were more frequently detected in the hair samples of the French women than in those of the Chinese women. In both cohorts, PCB 180 and BDE 47 were the dominant PCB and PBDE congener, respectively. PCB 180 was found in 82% of the French women and 44% of the Chinese women, while the corresponding values of BDE 47 were 54% and 11%, respectively. A discriminant analysis further demonstrated the difference in PCBs and PBDEs exposure profile between the two cohorts. These results demonstrate that hair analysis is sufficiently sensitive to detect exposure to these pollutants and highlight differences in exposure between populations even at environmental levels. Although BPA and BPS were found in 100% of the hair samples in both cohorts, the French women had significantly higher levels of BPA and BPS than the Chinese women. The median concentrations of BPA were one order of magnitude higher than BPS in both the Chinese (34.9 versus 2.84 pg/mg) and the French women (118 versus 8.01 pg/mg) respectively. Our results suggest that both French and Chinese populations were extensively exposed to BPA and BPS.

Maternal occupational exposure to carbonaceous nanoscale particles and small for gestational age and the evolution of head circumference in the French Longitudinal Study of Children - Elfe study.

OBJECTIVES: To investigate the association between exposure to unintentionally emitted carbonaceous nanoscale particles (NPs) and small for gestational age (SGA), as well as head circumference (HC) at birth and at two years of age. METHODS: Mothers from the French Longitudinal Study of Children (Elfe cohort) who worked during pregnancy were selected for our study. Data collected at birth and during follow-up (up to two years) were used. The probability and frequency of maternal occupational exposure to unintentionally emitted carbonaceous NPs was estimated using a job exposure matrix (MatPUF). Multivariate logistic regression, linear regression, and mixed models were applied to estimate any associations. Analyses were carried out depending on whether mothers stopped working during the first, second, or third trimester of pregnancy. RESULTS: Maternal occupational exposure to unintentionally emitted carbonaceous NPs was associated with SGA in the overall study population by multivariate analysis (ORa = 1.80, 95% CI: 1.29, 2.46), as well as in sub-groups of mothers who stopped working during the second (ORa = 1.84, 95% CI: 1.13, 3.02) or third (ORa = 1.80, 95% CI: 1.10, 2.95) trimesters. There were no significant associations with HC at birth or two years of age. CONCLUSIONS: We found a significant association between occupational exposure to carbonaceous NPs and SGA, with the effect depending on the period of exposure during pregnancy. These results should encourage further studies concerning the adverse effects of exposure to carbonaceous NPs on the development of offspring.

Indoor Microbiome: Quantification of Exposure and Association with Geographical Location, Meteorological Factors, and Land Use in France.

The indoor microbial community is a mixture of microorganisms resulting from outdoor ecosystems that seed the built environment. However, the biogeography of the indoor microbial community is still inadequately studied. Dust from more than 3000 dwellings across France was analyzed by qPCR using 17 targets: 10 molds, 3 bacteria groups, and 4 mites. Thus, the first spatial description of the main indoor microbial allergens on the French territory, in relation with biogeographical factors influencing the distribution of microorganisms, was realized in this study. Ten microorganisms out of 17 exhibited increasing abundance profiles across the country: Five microorganisms (Dermatophagoïdes pteronyssinus, Dermatophagoïdes spp., Streptomyces spp., Cladosporium sphaerospermum, Epicoccum nigrum) from northeast to southwest, two (Cryptococcus spp., Alternaria alternata) from northwest to southeast, Mycobacteria from east to west, Aspergillus fumigatus from south to north, and Penicillium chrysogenum from south to northeast. These geographical patterns were partly linked to climate and land cover. Multivariate analysis showed that composition of communities seemed to depend on landscapes, with species related to closed and rather cold and humid landscapes (forests, located in the northeast) and others to more open, hot, and dry landscapes (herbaceous and coastal regions, located in the west). This study highlights the importance of geographical location and outdoor factors that shape communities. In order to study the effect of microorganisms on human health (allergic diseases in particular), it is important to identify biogeographic factors that structure microbial communities on large spatial scales and to quantify the exposure with quantitative tools, such as the multi-qPCR approach.

Maternal cumulative exposure to extremely low frequency electromagnetic fields, prematurity and small for gestational age: a pooled analysis of two birth cohorts.

BACKGROUND: Data on the effects of extremely low frequency electromagnetic fields (ELF-EMF) on pregnancy outcomes are inconclusive. OBJECTIVE: To study the relation between maternal cumulative exposure to ELF-EMF during pregnancy and the risk of prematurity or small for gestational age (SGA) in a pooled analysis of two French birth cohorts. METHODS: Elfe and Epipage2 are both population-based birth cohorts initiated in 2011 and included 18 329 and 8400 births, respectively. Health data and household, mother and child characteristics were obtained from medical records and questionnaires at maternity and during follow-up. A job exposure matrix was used to assess cumulative exposure to ELF-EMF during three periods: (1) until 15 weeks of gestation, (2) until 28 weeks of gestation and (3) until 32 weeks of gestation. Analyses were restricted to single live births in mainland France and to mothers with documented jobs (N=19 894). Adjusted logistic regression models were used. RESULTS: According to the period studied, 3.2%-4% of mothers were classified as highly exposed. Results were heterogeneous. Increased risks of prematurity were found among low exposed mothers for the three periods, and no association was observed among the most exposed (OR1=0.92 (95% CI 0.74 to 1.15); OR2=0.98 (95% CI 0.80 to 1.21); OR3=1.14 (95% CI 0.92 to 1.41)). For SGA, no association was observed with the exception of increased risk among the low exposed mothers in period 2 and the most exposed in period 3 (OR=1.25 (95% CI 1.02 to 1.53)). CONCLUSION: Some heterogeneous associations between ELF-EMF exposure and prematurity and SGA were observed. However, due to heterogeneity (ie, their independence regarding the level of exposure), associations cannot be definitely explained by ELF-EMF exposure.

Multiple pesticides in mothers' hair samples and children's measurements at birth: Results from the French national birth cohort (ELFE).

BACKGROUND: A growing body of studies now suggests that the general population is continuously and ubiquitously exposed to numerous pesticides. However, studies investigating the possible role of environmental exposure to pesticides on fetal growth have focused on a limited set of substances, despite the hundreds of modern pesticides currently available. AIM: To explore the relation between maternal hair concentrations of 64 pesticides and metabolites and their newborns' measurements at birth, with data from the ELFE French nationwide birth cohort. METHODS: We measured 64 compounds (10-100% detection) in bundles of hair 9 cm long collected at birth from 311 women who gave birth in France in 2011. We assessed their associations with birth weight, length, and head circumference, adjusted for potential confounders, and used elastic net regularization to simultaneously select the strongest predictors of measurements at birth. Selected variables were multiply imputed for missing values, and unpenalized estimators were assessed by standard linear regression. RESULTS: We observed statistically significant associations between maternal hair concentrations of seven pesticides or pesticide metabolites and birth measurements (weight: fipronil sulfone; length: TCPy, bitertanol, DEP, and isoproturon; head circumference: tebuconazole and prochloraz). Analyses restricted to boys identified 12 additional compounds: 8 independently associated with birth weight (3Me4NP, DCPMU, DMST, fipronil, mecoprop, propoxur, fenhexamid, and thiabendazole), 2 with birth length (dieldrin and ß-endosulfan), and 6 with head circumference (ß-endosulfan, ß-HCH, fenuron, DCPMU, propoxur, and thiabendazole). CONCLUSION: Our results suggest that prenatal exposure to 19 pesticides or metabolites from various chemical families may influence measurements at birth. As with any exploratory research findings, results should be interpreted cautiously, until they are replicated or verified by further epidemiological or mechanistic studies.

Residential sources of pesticide exposure during pregnancy and the risks of hypospadias and cryptorchidism: the French ELFE birth cohort.

OBJECTIVES: Prenatal occupational exposure to pesticides has been associated with male reproductive tract abnormalities. Little is known about the possible impact of non-occupational pesticide exposure on fetal and child development in the general population. Using data from a nationwide birth cohort, we aimed to assess the association between residential sources of prenatal pesticide exposure and the risks of hypospadias and cryptorchidism. METHODS: Of the 9281 boys in ELFE (French Longitudinal Study of Children), the national French birth cohort, 53 were diagnosed with hypospadias and 137 with cryptorchidism. We assessed residential exposure sources from self-reported domestic use of eight types of pesticide products and French spatial land use data with acreage within a 1000 m radius around each family's home for 21 crop types. We used logistic regression modelling, adjusted for possible confounders that included estimated dietary pesticide intake. Multiple imputations were used to handle missing data. RESULTS: An increased risk of hypospadias was associated with domestic pesticide use against fleas and ticks (OR=2.28, 95% CI 1.09 to 4.75); no associations were found between cryptorchidism and any domestic pesticide use. Slightly increased risks of cryptorchidism were observed in association with all crop acreages near homes during pregnancy, especially for orchards, and no association was observed for hypospadias. CONCLUSIONS: Our results suggest a possible increased risk of hypospadias associated with prenatal use of some domestic pesticide products, likely to contain insecticides, and of cryptorchidism with nearby orchard acreage (crops repeatedly sprayed with pesticides). This work is limited by its modest number of cases.

Benefits of cooperation among large-scale cohort studies and human biomonitoring projects in environmental health research: An exercise in blood lead analysis of the Environment and Child Health International Birth Cohort Group.

A number of prospective cohort studies are ongoing worldwide to investigate the impact of foetal and neonatal exposures to chemical substances on child health. To assess multiple exposure (mixture) effects and low prevalence health outcomes it is useful to pool data from several studies and conduct mega-data-analysis. To discuss a path towards data harmonization, representatives from several large-scale birth cohort studies and a biomonitoring programme formed a collaborative group, the Environment and Child Health International Birth Cohort Group (ECHIBCG). In this study, an intra-laboratory trial was performed to harmonize existing blood lead measurements within the groups' studies. Then, decentralized analyses were conducted in individual countries' laboratories to evaluate blood lead levels (BLL) in each study. The measurements of pooled BLL samples in French, German and three Japanese laboratories resulted in an overall mean blood lead concentration of 8.66 µg l-1 (95% confidence interval: 8.59-8.72 µg l-1) with 3.0% relative standard deviation. Except for China's samples, BLL from each study were comparable with mean concentrations below or close to 10 µg l-1. The decentralized multivariate analyses revealed that all models had coefficients of determination below 0.1. Determinants of BLL were current smoking, age >35 years and overweight or obese status. The three variables were associated with an increase in BLL in each of the five studies, most strongly in France by almost 80% and the weakest effect being in Norway with only 15%; for Japan, with the far largest sample (~18,000), the difference was 36%. This study successfully demonstrated that the laboratory analytical methods were sufficiently similar to allow direct comparison of data and showed that it is possible to harmonize the epidemiological data for joint analysis. This exercise showed the challenges in decentralized data analyses and reinforces the need for data harmonization among studies.

Multiple pesticide analysis in hair samples of pregnant French women: Results from the ELFE national birth cohort.

BACKGROUND: A growing body of evidence suggests that prenatal exposure to pesticides might impair fetal development. Nonetheless, knowledge about pesticide exposure of pregnant women, especially in Europe, is largely restricted to a limited panel of molecules. AIM: To characterize the concentration of 140 pesticides and metabolites in hair strands from women in the ELFE French nationwide birth cohort. METHODS: Among cohort members who gave birth in northeastern and southwestern France in 2011, we selected those with a sufficient available mass of hair (n = 311). Bundles of hair 9 cm long were collected at delivery. We screened 111 pesticides and 29 metabolites, including 112 selected a priori based on their reported usage or detection in the French environment. The bundles of hair from 47 women were split into three segments to explore the intraindividual variability of the exposure. Intraclass correlation coefficients (ICCs) were computed for the chemicals with a detection frequency >70%. RESULTS: We detected a median of 43 chemicals per woman (IQR 38-47). Overall, 122 chemicals (>20 chemical families) were detected at least once, including 28 chemicals detected in 70-100% of hair samples. The highest median concentrations were observed for permethrin (median: 37.9 pg/mg of hair), p-nitrophenol (13.2 pg/mg), and pentachlorophenol (10.0 pg/mg). The ICCs for the 28 chemicals studied ranged from 0.59 to 0.94. CONCLUSION: Pregnant women are exposed to multiple pesticides simultaneously from various chemical families, including chemicals suspected to be reproductive toxicants or endocrine disruptors. The ICCs suggest that the intraindividual variability of pesticide concentrations in hair is lower than its interindividual variability.

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.

Is atmospheric pollution exposure during pregnancy associated with individual and contextual characteristics? A nationwide study in France.

BACKGROUND: Exposure to atmospheric pollutants is a danger for the health of pregnant mother and children. Our objective was to identify individual (socioeconomic and behavioural) and contextual factors associated with atmospheric pollution pregnancy exposure at the nationwide level. METHOD: Among 14 921 women from the French nationwide ELFE (French Longitudinal Study of Children) mother-child cohort recruited in 2011, outdoor exposure levels of PM2.5, PM10 (particulate matter <2.5 µm and <10 µm in diameter) and NO2 (nitrogen dioxide) were estimated at the pregnancy home address from a dispersion model with 1 km resolution. We used classification and regression trees (CART) and linear regression to characterise the association of atmospheric pollutants with individual (maternal age, body mass index, parity, education level, relationship status, smoking status) and contextual (European Deprivation Index, urbanisation level) factors. RESULTS: Patterns of associations were globally similar across pollutants. For the CART approach, the highest tertile of exposure included mainly women not in a relationship living in urban and socially deprived areas, with lower education level. Linear regression models identified different determinants of atmospheric pollutants exposure according to the residential urbanisation level. In urban areas, atmospheric pollutants exposure increased with social deprivation, while in rural areas a U-shaped relationship was observed. CONCLUSION: We highlighted social inequalities in atmospheric pollutants exposure according to contextual characteristics such as urbanisation level and social deprivation and also according to individual characteristics such as education, being in a relationship and smoking status. In French urban areas, pregnant women from the most deprived neighbourhoods were those most exposed to health-threatening atmospheric pollutants.