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International audience; 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 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 (OR(adjusted) = 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 (OR(adjusted) = 1.75; 95%CI: 1.11 to 2.75), a significantly lower birthweight for infants of mothers exposed to petroleum solvents (β(adjusted) = -47.37 g; -89.33 to -5.42), and a lower HC among newborns of those occupationally exposed to oxygenated solvents (β(adjusted) = -0.28; -0.49 to -0.07) and to chlorinated solvents (β(adjusted) = -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.

International audience; 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 β-endosulfan), and 6 with head circumference (β-endosulfan, β-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.

Background Testicular germ cell tumours (TGCT) are the most frequent cancers in young men in developed countries and their incidence rate has doubled worldwide over the past 40 years. Early life exposures to pesticides are suspected to increase TGCT risk. Our research aimed at estimating adult TGCT risk associated with parental domestic use of pesticides during early periods of child development. Methods We conducted a case-control study of 304 TGCT cases, aged 18–45 years old, recruited in 20 French university hospitals, and 274 controls frequency-matched on hospital and birth year. Participants’ mothers provided information on their domestic use of pesticides from 1 year before start of pregnancy to 1 year after their son’s birth, for gardening activities, treatment of indoor plants, pets, wood and mold, and pest control. Odds ratios (OR) for TGCT (overall and by histological subtype) and 95% confidence intervals (CI) were estimated using conditional logistic regression. Results Prevalence of reported domestic use of pesticides was 77.3% for insecticides, 15.9% for fungicides and 12.1% for herbicides. While no association was found for any use of insecticides (OR = 1.27, CI = 0.80–2.01) or herbicides (OR = 1.15, CI = 0.67–2.00), elevated risks of TGCT overall (OR = 1.73, CI = 1.04–2.87) and non-seminoma subtype (OR = 2.44, CI = 1.26–4.74) were observed for any use of fungicides. When specific purposes were examined, using fungicides and/or insecticides for woodwork (OR = 2.35, CI = 1.06–5.20) and using insecticides on cats and dogs (OR = 1.95, CI = 1.12–3.40) were associated with increased risk of non-seminoma subtype. We found no association for seminoma subtype. Conclusions Although recall bias may partially explain the elevated ORs, our study provides some evidence of a positive association between domestic use of pesticides during early periods of development, particularly fungicides and risk of adult TGCT and non-seminoma. Given the common domestic use of pesticides in France, further research on TGCT risk is warranted.

International audience; 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.

International audience; 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.

International audience; Introduction: Endocrine disruptors (ED) such as phthalates or bisphenol A are ubiquitous and pregnant women and children are particularly vulnerable. Perinatal health professionals are well-placed to inform pregnant women about the risks. We set out to evaluate perinatal health professionals' knowledge of ED and the information they give during pregnancy. Material and Methods: We invited midwives, obstetrician-gynecologists (OB/GYN), general practitioners (GP), and general medicine and OB/GYN residents to respond to a short Google survey between August and November 2018 by email using perinatal network. Results: Out of 4100 questionnaires sent, 1650 completed questionnaires were returned and analyzed. The participation rate was 41 % with the following distribution: midwives (n = 1215, 74 %), OB/GYN residents (n = 102, 6 %), OB/GYNs (n = 129, 8 %), GPs and residents in general medicine (n = 204, 12 %), in private and public hospitals in France. Only 181 of the respondents thought they were well-informed about ED including 160 midwives (11 %). Most of the responding professionals reported not to give any information during pregnancy (n = 946, 57.3 %). Midwives (n = 452, 37.2 %), people >50 years (n = 104, 41.6 %) and people working in private structures (n = 451, 34.9 %) were the most likely to give information, mainly orally. Overall, 346 (74.2 %) of the respondents considered that information about health risks of endocrine disruptors was important and most of them wished they were better informed (n = 1532, 92.9 %). Conclusion: Our study suggests that perinatal health professionals do not have enough medical information, training or tools to communicate about the risks associated with ED to pregnant women and consequently cannot educate them. Research is needed to further explore the risks and support prevention of environmental exposure for pregnant women. (C) 2020 Elsevier B.V. All rights reserved.

International audience; Since the mid-1950s, the definitions of normal labor set forth by E. Friedman have guided obstetric practices in maternity units across the globe. But recent work is challenging these definitions, now considered too restrictive and thought to induce excessive interventionism by medical professionals. The objective of this chapter of these Clinical Practice Guidelines is to redefine the structure and duration of normal labor, as well as the criteria defining abnormal labor. Based on a systematic review of the literature, we make various recommendations. In the first place, the diagnosis of labor dystocia is inappropriate during the latent phase. The active phase of the first stage of labor begins at a cervical dilation between 5 and 6 cm. On the other hand, a speed of dilation < 1 cm/4 h at the beginning of the active phase of the first stage is considered abnormal, as is a speed < 1 cm/2 h above 7 cm dilation. The maximum duration of the descent phase of the second stage of labor cannot be determined from the literature, but the risk-benefit balance becomes less favorable after 3 hours. Finally, the literature does not justify any recommendation about the maximum duration of the expulsion phase. These new guidelines should make it possible to reduce the rates of oxytocin use and of cesareans for labor dystocia.

ObjectivesPrenatal 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.MethodsOf 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.ResultsAn 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.ConclusionsOur 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.

Background: Glycol ethers (GE) are widely used organic solvents. Despite the potential neurotoxicity of several families of organic solvents, little is known about the impact of GE on the neurodevelopment of infants and children. Objectives: We investigated the relation between urinary concentrations of GE metabolites in pregnant women and neurocognitive abilities in their 6-year-old children in the PELAGIE mother–child cohort. Methods: Five GE metabolites were measured in first morning void urine samples of 204 French pregnant women in early pregnancy (< 19 weeks of gestation). Psychologists assessed the neurocognitive abilities of their 6-year-old children with the Wechsler Intelligence Scale for Children IV (WISC) and the Developmental Neuropsychological Assessment (NEPSY). We analyzed the results with linear (WISC) and Poisson regression models (NEPSY), adjusted for potential confounders, including child’s stimulation at home. Results: GE metabolites were detected in 90–100% of maternal urine samples. The WISC Verbal Comprehension score was significantly lower for children with the highest tertile of urinary phenoxyacetic acid (PhAA) [β (third vs. first tertile) = –6.53; 95% CI: –11.44, –1.62]. Similarly, the NEPSY Design Copying subtest score was lower in those with the highest tertile of urinary ethoxyacetic acid (EAA) [β (third vs. first tertile) = –0.11; 95% CI: –0.21, 0.00]. The other GE metabolites we studied were not significantly associated with WISC or NEPSY scores. Conclusions: Prenatal urine concentrations of two GE metabolites were associated with lower WISC Verbal Comprehension Index scores and NEPSY Design Copying subscale scores, respectively, at age 6 years. PhAA is the primary metabolite of 2-phenoxyethanol (EGPhE), which is commonly found in cosmetics, and precursors of EAA are frequently used in cleaning agents. Additional research is needed to confirm our findings and further explore potential effects of prenatal GE exposures on neurocognitive performance in children. Citation: Béranger R, Garlantézec R, Le Maner-Idrissi G, Lacroix A, Rouget F, Trowbridge J, Warembourg C, Monfort C, Le Gléau F, Jourdin M, Multigner L, Cordier S, Chevrier C. 2017. Prenatal exposure to glycol ethers and neurocognitive abilities in 6-year-old children: the PELAGIE cohort study. Environ Health Perspect 125:684–690; http://dx.doi.org/10.1289/EHP39

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. Keywords: Maternal exposure, Pesticides, Hair, Environmental monitoring

Background/aim Prenatal occupational exposure to pesticides has been associated to congenital malformations, but little is known about the effect of dietary exposure in the general population. Exposure to various pesticides through dietary intake has been recently assessed in French pregnant women. We aimed to study its association with the risk of hypospadias. Methods Among 7035 boys enrolled in 2011 the French national birth cohort Elfe, 46 have been diagnosed with hypospadias. Maternal daily intakes were estimated for 317 pesticides, based on a validated self-administered food frequency questionnaire combined with data of national monitoring programs on pesticide residues in food. Among those with non-null daily intake in >10% women (n=105), we focused on substances (n=60) with suspected endocrine disrupting properties or susceptible to impair the development of male reproductive organs. We used logistic regression to assess the risk of hypospadias in association with the dietary daily intake of 1) pesticides grouped by chemical family, or 2) individual pesticides selected a priori as the best predictors using cross-validated Elastic-Net model. Results An increased risk of hypospadias was found statistically significant for the group of anilinopyrimidine pesticides (3rd vs 1 st and 2nd tertiles of exposure; OR=2.26, 95% CI: 1.25 to 4.11), for the organochlorine pesticides family (3rd vs 1 st and 2nd tertiles; OR=2.16, 1.20; 3.91) and for the group of amide pesticides (3rd vs 1 st and 2nd tertiles; OR=1.95, 1.08; 3.52). Three individual pesticides (among 60) were selected by the Elastic-Net procedure and showed increased risk of hypospadias for λ-cyhalothrin (3rd vs 1 st and 2nd tertiles, OR=2.34, 1.26; 4.42) and for cyprodinil (3rd vs 1 st and 2nd tertiles; OR=1.66, 0.90; 3.10) and DDT (3rd vs 1 st and 2nd tertiles; OR=1.72, 0.95; 3.15). Conclusion Although the number of cases is small, our results are consistent with existing literature that have suggested increased risk of hypospadias in association with organochlorine pesticides. A confirmation with biomonitoring data would be give strength to the results.

International audience; Purpose of review - The use of pesticides is predominant in agriculture, inducing environmental contamination, and has been extended to the domestic sphere. In France, > 500 pesticides were authorized for use in 2009; given their various toxicological properties, there are legitimate concerns about the possible consequences for child health. This review summarizes the recent French studies of good quality dealing with pesticides and child health. Recent findings - Three cohorts (mother-child, retrospective) and two case-control studies have been conducted in the last decade. Using various instruments for exposure assessment including biomarkers, they have suggested alterations of subclinical health parameters at birth, increased risk of otitis at age 2, and increased risk of several types of childhood cancer. However, there were no adverse neurodevelopmental outcomes at 6 years of age following prenatal exposure to pesticides. Both agricultural and domestic pesticides might be involved in such adverse health outcomes. Similar studies are lacking in Europe. Studies on fungicides and child health are scarce.

Objectives A potential impact of exposure to endocrine disruptors, including pesticides, during intrauterine life, has been hypothesised in testicular germ cell tumour (TGCT) aetiology, but exposure assessment is challenging. This large-scale registry-based case–control study aimed to investigate the association between parental occupational exposure to pesticides and TGCT risk in their sons. Methods Cases born in 1960 or onwards, aged between 14 and 49 years, and diagnosed between 1978 and 2013 in Denmark, Finland, Norway or Sweden, were identified from the respective nationwide cancer registries. Four controls per case were randomly selected from the general national populations, matched on year of birth. Information on parental occupation was collected through censuses or Pension Fund information and converted into a pesticide exposure index based on the Finnish National Job-Exposure Matrix. Results A total of 9569 cases and 32 028 controls were included. No overall associations were found for either maternal or paternal exposures and TGCT risk in their sons, with ORs of 0.83 (95% CI 0.56 to 1.23) and of 1.03 (0.92 to 1.14), respectively. Country-specific estimates and stratification by birth cohorts revealed some heterogeneity. Cryptorchidism, hypospadias and family history of testicular cancer were risk factors but adjustment did not change the main results. Conclusions This is the largest study on prenatal exposure to pesticides and TGCT risk, overall providing no evidence of an association. Limitations to assess individual exposure in registry-based studies might have contributed to the null result.

Introduction: We previously found prenatal solvent exposures at higher risk of externalizing disorders in 2-year-old children, consistently with animal data and the few existing study in human. We ...

Testicular germ cell tumors (TGCT) represent the most frequent cancer in men aged between 15 and 45 years. Current hypotheses are focusing on environmental exposures occurring during prenatal periods. However, very few studies have explored intra-uterine environmental exposure related to TGCT. TESTEPERA is a pilot case-control study aiming to determine the effectiveness of different recruitment approaches in the French context and to verify our ability to collect relevant data on their prenatal periods. Between 2011 and 2012, 150 male subjects were contacted in the Rhône-Alpes region (58 cases from a cancer center and 92 controls from a regional maternity). Participation rate varied from 33% for cases diagnosed in 2008 vs 68% for cases diagnosed in 2010. Participation rate of controls varied depending on modalities of contact (13% for face-to-face recruitment; 0% for contact by phone only; 50% for face-to-face contact with phone reminder). Data collection allowed precise job identification and geolocation of subjects' addresses. Precision of geolocation was dependent upon the level of urbanization (p0.001) but not on the time period (p = 0.52). Our results support the feasibility of a case-control study focusing on the relation between TGCT and environmental pesticide exposures during early and later life.

Background Testicular germ cell tumours (TGCT) are the most common cancers in men aged between 15 and 44 years and the incidence has increased steeply over the past 30 years. The rapid increase in the incidence, the spatial variation and the evolution of incidence in migrants suggest that environmental risk factors play a role in TGCT aetiology. The purpose of our review is to summarise the current state of knowledge on occupational and environmental factors thought to be associated with TGCT. Methods A systematic literature search of PubMed. All selected articles were quality appraised by two independent researchers using the ‘Newcastle-Ottawa Quality Assessment Scale’. Results After exclusion of duplicate reports, 72 relevant articles were selected; 65 assessed exposure in adulthood, 7 assessed parental exposures and 2 assessed both. Associations with occupation was reported for agricultural workers, construction workers, firemen, policemen, military personnel, as well as workers in paper, plastic or metal industries. Electromagnetic fields, PCBs and pesticides were also suggested. However, results were inconsistent and studies showing positive associations tended to had lower quality ranking using the assessment scale (p=0.02). Discussion Current evidence does not allow concluding on existence of any clear association between TGCT and adulthood occupational or environmental exposure. The limitations of the studies may partly explain the inconsistencies observed. The lack of association with adulthood exposure is in line with current hypotheses supporting the prenatal origin of TGCT. Future research should focus on prenatal or early life exposure, as well as combined effect of prenatal and later life exposure. National and international collaborative studies should allow for more adequately powered epidemiological studies. More sophisticated methods for assessing exposure as well as evaluating gene–environment interactions will be necessary to establish clear conclusion.

Background The incidence of testicular germ cell tumors (TGCT), the most common cancer in men aged 15 to 45 years, has doubled over the last 30 years in developed countries. Reasons remain unclear but a role of environmental factors, especially during critical periods of development, is strongly suspected. Reliable data on environmental exposure during this critical time period are sparse. Little is known on whether it could be a combined effect of early and later-life exposures. Methods/Design Our research aims to study the association between TGCT risk and pesticide exposures (domestic, occupational and environmental) during critical time periods of development and combined early and later-life exposures. The study design, developed during a 2-year pilot study, is a multicenter case–control study of 500 cases (ascertained through histology) and 1000 fertile/fecund controls recruited through 21 French ‘Centres d’Etude et de Conservation des Œufs et de Sperme humain’ (CECOS). Trained professional interviewers interview the subjects and their mothers by phone. Using a geographic information system developed and tested for application in this study design, environmental pesticides exposure assessment is based on life-time residential history. Occupational pesticides exposures are assessed by an industrial hygienist based on parents’ occupations and tasks. Exposures during the prenatal period, early childhood and puberty are focused. A blood sample is collected from each participant to assess genetic polymorphisms known to be associated with TGCT risk, as well as to explore gene-environment interactions. Discussion The results of our study will contribute to better understanding the causes of TGCT and the rapid increase of its incidence. We explore the effect of combined early and later-life pesticides exposure from multiple sources, as well as potential gene-environment interactions that have until now been rarely studied for TGCT. Our design allows future pooled studies and the bio-bank allows additional genetic or toxicological analyses.