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International audience; OBJECTIVE: The objective was to assess the predictive value of head-perineum distance measured at the initiation of the active second stage of labor on the mode of delivery. MATERIAL AND METHODS: It was a prospective cohort study in an academic Hospital of Rennes, France, from July 1, 2020 to April 4, 2021 including 286 full-term parturients who gave birth to a newborn in cephalic presentation. A double-blind ultrasound measurement of the head-perineum distance was performed during the second phase of labor within five minutes after the onset of pushing efforts. The primary outcome was the mode of delivery (spontaneous vaginal delivery versus instrumental vaginal delivery or cesarean section). We performed a multivariate analysis to determine the predictive value of the head-perineum distance by adjusting on potential confounders. RESULTS: Overall, 199 patients delivered by spontaneous vaginal delivery, 80 by instrumental vaginal delivery, and seven by cesarean section. The head-perineum distance measured at the beginning of pushing efforts was predictive of the mode of delivery with a threshold at 44 mm (crude: sensitivity = 56.8 % and specificity = 79.3 %; adjusted: sensitivity = 79.4 % and specificity = 87.4 %). The risk of medical intervention was higher when the head-perineum distance is>44 mm with an adjusted OR of 2.78 [1.38; 5.76]. CONCLUSION: The head-perineum distance measured at the initiation of the active second stage of labor is predictive of the mode of delivery. Head-perineum distance below 44 mm predicts a vaginal delivery with the best diagnostic performance, and optimizes the time to start pushing efforts.

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; 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.

International audience; We conducted a literature review focusing on the use and health effects of cosmetics, especially among pregnant and lactating women and young children. Based on these data, we propose clinical practice guidelines for health care professionals to use for informing and advising their patients. These include the recommendations that families: (1) reduce the number and the frequency of use (grade B) and the amount applied (expert consensus) of all cosmetic products during the perinatal period and among children; (2) prefer simple, fragrance-free, and rinsable products, with short ingredient lists (expert consensus); and (3) for children, avoid industrial wipes and prefer water, with suitable soap when necessary. © 2022 by the American College of Nurse-Midwives.

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.

Ces recommandations de pratique clinique (RPC) ont pour but de définir les messages et les interventions de prévention à délivrer aux femmes et aux co-parents par les différents professionnels de la périnatalité. Les recommandations sont divisées en dix chapitres, réparties sur quatre axes : 1/ l’adaptation des comportements maternels (activité physique, substances psychoactives) ; 2/ les comportements alimentaires ; 3/ l’exposition domestique aux agents toxiques (usages domestiques, cosmétiques) ; 4/ la promotion de la santé de l’enfant (allaitement maternel, liens d’attachement, écrans, mort inattendue du nourrisson, syndrome du bébé secoué). Une hiérarchie des différents messages de prévention a été proposée selon les périodes afin de tenir compte des contraintes de temps rencontrées par les professionnels.

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; Background: A growing body of evidences suggests an association between early exposure to organophosphates (OPs), organochlorines (OCs), pyrethroids or carbamates and autism spectrum disorder (ASD). However, there are limited data about the other pesticide groups, especially in Europe. Objectives: Based on a systematic review, we aimed to assess the influence of neuro- and thyrotoxic agricultural and domestic pesticides (other than OPs, OCs, pyrethroids and carbamates) authorized in Europe on risk of ASD in children or ASD behavioral phenotypes in rodents. Methods: Pesticides were initially identified in the Hazardous Substances Data Bank. 20 currently used (10 pesticide groups) were retained based on the higher exposure potential. Epidemiological (children) and in vivo (rodents) studies were identified through PubMed, Web of Science and TOXLINE, without restriction of publication date or country (last update: November 2019). The risk of bias and level of evidence were also assessed. This systematic review is registered at the International Prospective Register of Systematic Reviews (PROSPERO, registration number CRD42019145384). Results: In total, two epidemiological and 15 in vivo studies were retained, focusing on the azole, neonicotinoid, phenylpyrazole and phosphonoglycine pesticide groups. No study was conducted in Europe. Glyphosate, imidacloprid, clothianidin, myclobutanil, acetamiprid, tebuconazole, thiabendazole and fipronil, globally reported an association with an increased risk of ASD in children and/or ASD behavioral phenotypes in rodents. In children, glyphosate and myclobutanil showed a “moderate level of evidence” in their association with ASD, whereas imidacloprid showed an “inadequate level of evidence”. In rodents, clothianidin, imidacloprid and glyphosate showed a “high level of evidence” in their association with altered behavioral, learning and memory skills. Conclusion: In the framework of environmental risk factors of ASD, novel hypotheses can be formulated about early exposure to eight pesticides. Glyphosate presented the most salient level of evidence. Given their neuro- and thyrotoxic properties, additional studies are needed for the 12 other pesticides not yet studied as potential ASD risk factors according to our inclusion criteria.

International audience

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.

Introduction Les expositions prenatales aux pesticides sont frequemment associees a un risque eleve de trouble du spectre autistique (TSA) chez les enfants. A ce jour, aucune etude n’a investigue l’influence de ces expositions sur le pronostic clinique des enfants avec TSA. L’objectif de cette etude est donc d’analyser les associations entre la proximite residentielle aux parcelles agricoles pendant la grossesse et les comportements adaptatifs des enfants avec TSA. Methodes Nous avons inclus 183 enfants avec un diagnostic certain de TSA provenant de la cohorte francaise ELENA (Etude longitudinale de l’enfant avec autisme). Les comportements adaptatifs ont ete evalues a l’aide de la deuxieme edition de la « Vineland Adaptive Behavior Scales » (VABS-II). Les sous-scores de la VABS-II (communication, competences de la vie quotidienne et socialisation) a l’inclusion des enfants dans la cohorte ELENA ont ete consideres. A l’aide des donnees d’utilisation des sols du « Corine Land Cover » ( https://www.eea.europa.eu/fr ) et d’un logiciel de systeme d’information geographique, nous avons mesure les surfaces agricoles dans un rayon de 1000 m autour des domiciles des meres pendant leur grossesse. Des modeles de regressions lineaires ont ete utilises pour analyser les associations. Resultats L’âge moyen (ecart-type) des enfants a l’inclusion dans la cohorte ELENA etait de 6(3) ans, 39 % d’entre eux presentaient une deficience intellectuelle (DI). Les scores moyens a la VABS-II etaient de 73,0 (15,8), 74,8 (13,6) et 71,8 (11,3) respectivement pour les sous-domaines de la communication, des competences de la vie quotidienne et la socialisation. Ces sous-scores etaient plus eleves chez les enfants sans DI. En moyenne, la surface agricole couvrait 29 (27) % de la superficie formee par le rayon de 1000 m autour des domiciles. Les niveaux d’expositions aux parcelles agricoles etaient similaires entre les sous-groupes d’enfants avec et sans DI. Pendant la grossesse, chaque augmentation de 20 % de la surface agricole autour des domiciles etait associee a une diminution significative du score de communication a la VABS-II chez les enfants sans DI (β= −2,21, IC95 % : −4,16 a −0,27). Aucune association n’a ete trouvee chez les enfants avec DI (Tableau 1). Conclusion Il s’agit de la premiere etude conduite chez les enfants avec TSA montrant une association entre une proximite residentielle aux parcelles agricoles, mesure indirecte de l’exposition aux pesticides agricoles, et les troubles des comportements adaptatifs. Tableau 1: http://extranet.insight-outside.fr/upload/compte1352/Base/inscriptions_projets/image/99898-image.pdf

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.

Resume Depuis le milieu des annees 1950, les definitions du travail normal etablies par E. Friedman ont servi de reference pour guider la pratique obstetricale dans les maternites a travers le monde. Mais des travaux recents remettent en question ces definitions, considerees comme trop restrictives et induisant un interventionnisme excessif de la part des soignants. L’objectif de ce chapitre des recommandations pour la pratique clinique (RPC) etait de redefinir la structure et la duree du travail normal, ainsi que les criteres definissant un travail anormal. A partir d’une revue systematique de la litterature, differentes recommandations ont ete produites. En premier lieu, le diagnostic de dystocie du travail est inapproprie au cours de la phase de latence. Le debut de la phase active du 1er stade du travail est etabli entre 5 et 6 cm de dilatation cervicale. D’autre part, la vitesse de dilatation est consideree comme anormale si

Pesticides have been associated with various pathologies, and there is growing evidence of pesticide presence in domestic environments. However, most available studies focused on a limited number of pesticides or households, and few have been conducted in Europe. We aimed to assess indoor pesticide contamination by screening the prevalence of 276 pesticides and ten pesticide metabolites, in French households from different agricultural and urban areas. We sampled indoor dust from 239 households in 2012, proximate to orchards (n = 69), cereals (n = 66) and vineyard (n = 68) crops, or from urban area (n = 36). we used cellulose wipes moistened with isopropanol and polypropylene dust traps to collect recent (7 and 30 days, respectively) and settled dust (6 months). Overall, 125 pesticides and piperonyl butoxide were detected at least once in households, mostly at low prevalence: 97 in recent dust, and 111 in settled dust. In recent dust, the most prevalent compounds were o-phenylphenol (168 households, 70%), pentachlorophenol (86, 36%), and piperonyl butoxide (82, 34%). In addition to agricultural pesticides, we found a high proportion of domestic and banned compounds in recent and settled house dust. Several pesticides were identified in house dust, from different pesticide groups and sources. Our results suggest that domestic usage and persistence of banned pesticides may contribute substantially to indoor pesticide contamination. Graphical abstract 97 pesticides detected in households' recent indoor dust.

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.

Background/aim There are concerns neuro-developmental due to exposure to endocrine disrupting chemicals. Previous epidemiological studies have mainly focused on phthalate metabolites and bisphenol A. Our study aimed to assess associations between in-utero exposure to the afore mentioned compounds and other ubiquitous phenolic compounds and the Intelligence Quotient (IQ) of boys at 5–6 years. Methods In 452 mother-son dyads from the French EDEN cohort, we measured 11 phthalate metabolites and 9 phenolic compounds (4 parabens, benzophenone-3, bisphenol A, 2 dichlorophenols and triclosan) in spot urine samples collected between 22 and 29 gestational weeks. Verbal and performance IQ of children was assessed at 5–6 years by a psychologist using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI). We used adjusted Structural Equation Models (SEM) and the Benjamini and Hochberg false discovery rate (FDR) correction to assess the associations between maternal urine phenol and phthalate metabolite concentrations considered simultaneously and the boys’ IQ. Results No phenol or phthalate metabolite concentration was negatively associated with child verbal or performance IQ (p-values≥0.09). Mono (3-carboxypropyl) phthalate tended to be associated with increased verbal IQ (β=0.136, 95% confidence interval, 0.01; 0.27) but this association disappeared after correction for multiple comparison (corrected p- 64 value, 0.71). Conclusion To our knowledge, our study is the first to consider developmental exposure to parabens, dichlorophenols, triclosan and benzophenone-3 in relation to child cognitive development. Our findings did not suggest an inverse association between in-utero phenols and phthalates exposure and child verbal and performance IQ.

Motivation At the same time that toxicologists express increasing concern about reproducibility in this field, the development of dedicated databases has already smoothed the path toward improving the storage and exchange of raw toxicogenomic data. Nevertheless, none provides access to analyzed and interpreted data as originally reported in scientific publications. Given the increasing demand for access to this information, we developed TOXsIgN, a repository for TOXicogenomic sIgNatures. Results The TOXsIgN repository provides a flexible environment that facilitates online submission, storage and retrieval of toxicogenomic signatures by the scientific community. It currently hosts 754 projects that describe more than 450 distinct chemicals and their 8491 associated signatures. It also provides users with a working environment containing a powerful search engine as well as bioinformatics/biostatistics modules that enable signature comparisons or enrichment analyses. Availability and implementation The TOXsIgN repository is freely accessible at http://toxsign.genouest.org. Website implemented in Python, JavaScript and MongoDB, with all major browsers supported. Supplementary information Supplementary data are available at Bioinformatics online.

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.

International audience

Introduction: L’impact de l’environnement sur la grossesse semble maintenant bien etabli. Certaines expositions a des agents chimiques, mais aussi biologiques et physiques peuvent impacter le deroulement de la grossesse tout comme le developpement du fœtus. Cet article a pour but de synthetiser les connaissances sur le sujet. Methode: Une revue de la litterature a ete conduite a partir d’une recherche ciblee sur la base de donnees Medline. Resultats: Les donnees de la litterature font etat de risques de malformations, de troubles de la croissance ou encore de troubles du developpement neurologique. Les repercussions des expositions subies au cours de la grossesse peuvent se ressentir a la naissance, durant l’enfance, mais aussi pendant la vie adulte, voire sur les generations suivantes. Discussion: Des moyens de preventions peuvent etre mis en place pour limiter certaines expositions domestique, professionnelles ou comportementales. Tout en insistant sur ces moyens de prevention, il est necessaire de bien rappeler que la frequence d’issues defavorables de la grossesse reste faible, au regard de l’exposition quasi systematique des femmes a un large panel d’agents reprotoxiques.

Resume Position du probleme Les tumeurs germinales du testicule (TGCT) sont le principal cancer de l’homme jeune. Des facteurs environnementaux survenant au cours des periodes prenatales sont suspectes, mais tres peu d’etudes ont ete conduites. Methodes TESTEPERA est une etude pilote cas-temoins visant a evaluer differentes approches pour le recrutement des sujets en France ainsi que notre capacite a recueillir les donnees necessaires pour evaluer leurs expositions prenatales. Resultats Entre 2011et 2012, 150hommes ont ete contactes en Rhone-Alpes (58cas dans un centre de lutte contre le cancer et 92temoins dans une maternite regionale). Les taux d’acceptation des cas variaient de 33% pour ceux diagnostiques en 2008a 68% pour ceux diagnostiques en 2010. Le taux d’acceptation des temoins etait de 13% pour ceux rencontres physiquement, 0% pour ceux contactes par telephone uniquement, et 50% pour ceux rencontres physiquement et relances par telephone. Les donnees recueillies ont permis l’identification des metiers exerces. Quatre-vingt-deux pour cent des adresses etaient geolocalisees precisement. La precision dependait du niveau d’urbanisation ( p p =0,52). Conclusion Nos resultats confirment la faisabilite d’une etude cas-temoins etudiant la relation entre les TGCT et l’exposition environnementale precoce ou tardive aux pesticides.

Background Testicular cancer mainly affects White Caucasian populations, accounts for 1% of all male cancers, and is frequently the most common malignancy among young adult men. In light of the escalating rates of testicular cancer incidence in Europe, and in support of future planning to ensure optimal care of patients with what can be a curable disease, we predict the future burden in 40 European countries around 2025. Methods Current observed trends were extrapolated with the NORDPRED model to estimate the future burden of testicular cancer in the context of changes in risk versus changes in demographics. Findings Despite substantial heterogeneity in the rates, the vast majority of European countries will see an increasing burden over the next two decades. We estimate there will be 23,000 new cases of testicular cancer annually in Europe by 2025, a rise of 24% from 2005. Some of the most rapid increases in testicular cancer are observed in Croatia, Slovenia, Italy and Spain, and a transition is underway, whereby recent attenuations and declines in rates in certain high-risk countries in Northern Europe contrast with the increasing trends and escalating burden in Southern Europe. According to our estimates for 2025, around one in 100 men will be diagnosed with the disease annually in the highest risk countries of Europe (Croatia, Slovenia and Norway). Interpretation Elucidating the key determinants of testicular cancer and the equitable provision of optimal care for patients across Europe are priorities given the steady rise in the number of patients by 2025, and an absence of primary prevention opportunities. Funding None.

La concentration en HbL dans le produit issu de la RSPO n’est pas negligeable. Les objectifs de cette etude etaient de rechercher les facteurs influencant les variations du taux d’HbL et d’evaluer son impact sur la fonction renale. Methode Au CHU, de 2007 a 2016, 427 patients ont beneficie d’un controle qualite lors d’une RSPO. Au total, 243 patients ont ete inclus dans l’etude (chirurgie cardiaque + CEC, sauf dossiers incomplets et mineurs). Deux types de machines ont ete utilisees (CATS® puis Elite® a partir de 2014). Le taux d’HbL est exprime en G.L−1 et la quantite totale d’HbL en G (= taux d’HbL × volume transfuse). Depuis 2011, l’HbL est dosee par spectrophotometrie (TIETZ). L’impact sur la fonction renale de la quantite d’HbL injectee a ete mesure a partir des donnees 2011–2017. Les analyses ont ete realisees avec le logiciel SAS v9,4. Une regression lineaire multivariee a ete conduite pour etudier la relation entre la quantite d’HbL et les parametres de la fonction renale a J1 et J3 (creatinemie et clearance MDRD). Resultats Les donnees sur la periode 2007–2016 sont reportees dans le Tableau 1. Le taux d’HbL n’est pas correle avec l’âge du patient, le type de chirurgie, le volume recueilli ou le type de machine. La quantite d’HbL augmente significativement avec la duree de CEC ( Tableau 1 ). La moyenne du taux d’HbL est significativement plus elevee pour la periode 2011–2016 (2,01 vs. 1,42 en 2007–2010). Les valeurs de la creatinemie ou de la clearance a J1 et J3 ne sont pas correlees a la quantite d’HbL contenue dans le produit. Conclusion La quantite d’HbL dans le produit transfuse n’est pas negligeable et est liee a la duree de la CEC, mais nous ne pouvons definir a partir de quelle duree un lavage plus long serait necessaire. Toute etude cherchant a evaluer les consequences de l’injection d’HbL doit preciser la methode de mesure utilisee car elle impacte les resultats. Dans notre etude, la quantite d’HbL injectee ne semble pas avoir de retentissement renal a court terme.

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 ...

Objectifs L’objectif principal de notre etude etait de mesurer l’impact de la prise de poids pendant la grossesse sur la variete de presentation a l’expulsion. Les objectifs secondaires etaient de mesurer l’impact de l’indice de masse corporelle (IMC) et de la taille maternelle sur la variete de presentation a l’expulsion. Materiel et methode Nous avons realise une etude cas-temoins bicentrique retrospective incluant 130 degagements en occipito-sacre (OS) et 390 en occipito-pubien (OP). L’impact de la prise de poids, de l’IMC et de la taille sur la probabilite de degagement en OS a ete teste et quantifie par un modele de regression logistique. Nous avons utilise le logiciel R et la bibliotheque Epi pour realiser nos differents tests. Resultats Notre etude a montre qu’a partir de 12 kg, chaque kg supplementaire augmentait de 14 % le risque de degagement en OS (OR, 1,145, IC a 95 % [1,068–1,227]). La probabilite d’OS augmentait quand l’IMC etait plus eleve (OR = 1,12, IC a 95 % [1,07–1,17]). Conclusion Une prise de poids excessive pendant la grossesse peut entrainer de nombreuses complications fœto-maternelles et favoriser un degagement en OS. Il est essentiel de depister et prevenir ces facteurs de risque pendant la grossesse ainsi que de diagnostiquer les varietes posterieures persistantes en salle de naissance.

Introduction Exposure to pesticides has been suggested as a risk factor for several diseases or adverse health outcomes. The use of geographic information systems (GIS) in epidemiological studies to y to assess environmental exposure to agricultural pesticides (EEAP) is growing. Residential proximity to agricultural crops is frequently used as a surrogate of EEAP. Previous studies have suggested that application of pesticides near residences results in contamination of indoor surfaces. US studies have recently reported a positive correlation between the proximity or crop acreage and the contamination of indoor dust by agricultural pesticides in nearby homes. There is however no validated and applicable model in France: the US model is based on pesticide use registries and adapted on large crops and local practices. However, most of these studies did not consider spatial information on environmental factors such as wind direction and physical barriers (structural or natural) to pesticide drift from the field to receptors. In France, the availability of public data on these aspects allows to describe the relationship between the proximity of agricultural areas and residential exposure to pesticides. We aimed to assess geographical determinants of the indoor dust contamination by agricultural pesticides in different crop areas (SIGEXPO project). Methods A GIS was developed for 239 households, from three different agricultural sectors (69 near orchards and cereals, 66 near cereals, 68 near vineyards) and an urban area (n = 36). For each residence, the GIS considers the agricultural land use, the proximity of household to agricultural zones (fields). For five different buffer sizes (250 m–1250 m), we used GIS to determine targeted crop acreage, prevailing winds, and vegetative, topographic and structural barriers to pesticides drift from crops. Two additional dimensions have been considered in the development of the GIS: prevailing winds direction that influence pesticide drift and obstacles that mitigate on pesticide drift from agricultural applications, i.e. the presence of topographical, vegetal (hedges, forests) or structural barriers (built areas). The effect of obstacles is reflected in the presence of topographical, vegetal (hedges, forests) or structural barriers (built areas). In parallel, both recent ( 6 month) indoor dust samples were collected from households without professional pesticide users and analyzed. Pesticide applicators were excluded from the study. Information household characteristics and domestic pesticide users were collected by questionnaire. Redundancy analyzes were conducted to define the geographical determinants that best explain the indoor dust concentrations of the 27 agricultural pesticides detected in more than 10% of study households. Results Overall, main determinants of agricultural pesticides contamination in indoor dust were crop acreage within 500 m (orchards) or 1000 m buffer size (vineyards and cereals), as well as prevailing winds, and the presence of vegetative barriers. Our different models explained up to 18.3% of the variability of the pesticide contamination in indoor dust. Conclusion While the explained variability remains modes overall, it was above or comparable to previous studies. The determinants identified should be taken into account in future GIS-based approaches aiming to assess EEAP in the French context. The approach developed to assess the impact of wind and barriers need to be validated on additional datasets. Future studies should include the analyses of the impact of seasonal variations into the geographical determinants selection.

International audience; Pesticides and polychlorinated biphenyls (PCBs) are commonly found in house dust and have been described as a valuable matrix to assess indoor pesticide and PCB contamination. The aim of this study was to assess the efficiency and precision of cellulose wipe for collecting 48 pesticides, eight PCBs, and one synergist at environmental concentrations. First, the efficiency and repeatability of wipe collection were determined for pesticide and PCB residues that were directly spiked onto three types of household floors (tile, laminate, and hardwood). Second, synthetic dust was used to assess the capacity of the wipe to collect dust. Third, we assessed the efficiency and repeatability of wipe collection of pesticides and PCB residues that was spiked onto synthetic dust and then applied to tile. In the first experiment, the overall collection efficiency was highest on tile (38%) and laminate (40%) compared to hardwood (34%), p

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.

Premature ovarian failure (POF) is a cause of infertility that affects about 1% of women under 40, and is considered as idiopathic in 75% of cases. An occupational chemical origin has been identified at least once with 2-bromopropane, but human studies are rare and experimental data are sparse. This review aims to carry out a critical synthesis of knowledge of the chemical agents likely to affect follicular stock in humans and/or animals, by direct toxicity to follicles, or by increasing their recruitments. Of 140 chemical agents (or groups) studied, 20 have been identified as potentially damaging to the ovarian reserve. For the majority of toxic agents, only experimental data are currently available. At least four of these agents are likely to lead to POF in descendents (ethylene glycol methyl ether; 2,2-bis(bromomethyl)-1,3-propanediol; benzo[a]pyrene; dimethylbenzantracene). We propose a strategy aiming to encourage progress in identifying occupational factors responsible for POF.

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.