Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Low-level exposure to polychlorinated biphenyl-153 (PCB-153) and dichlorodiphenyldichloroethylene (p-p'-DDE) can impair fetal growth; however, the exposure-response relationship and effect modifiers of such association are not well established. This study is an extension of an earlier European meta-analysis. Our aim was to explore exposure-response relationship between PCB-153 and p-p'-DDE and birth outcomes; to evaluate whether any no exposure-effect level and susceptible subgroups exist; and to assess the role of maternal gestational weight gain (GWG). We used a pooled dataset of 9377 mother-child pairs enrolled in 14 study populations from 11 European birth cohorts. General additive models were used to evaluate the shape of the relationships between organochlorine compounds and birth outcomes. We observed an inverse linear exposure-response relationship between prenatal exposure to PCB-153 and birth weight [decline of 194g (95% CI -314, -74) per 1μg/L increase in PCB-153]. We showed effects on birth weight over the entire exposure range, including at low levels. This reduction seems to be stronger among children of mothers who were non-Caucasian or had smoked during pregnancy. The most susceptible subgroup was girls whose mothers smoked during pregnancy. After adjusting for absolute GWG or estimated fat mass, a reduction in birth weight was still observed. This study suggests that the association between low-level exposure to PCB-153 and birth weight exists and follows an inverse linear exposure-response relationship with effects even at low levels, and that maternal smoking and ethnicity modify this association.
ISSN: 0160-4120

hal-01118572
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01118572
PUBMED : 25314142
DOI : 10.1016/j.envint.2014.09.013

Éditeur(s) : HAL CCSD
Résumé : Publié en septembre 2013 dans le "Journal de Gynécologie Obstétrique et Biologie de la Reproduction" vol.42 n°5 p.413-444
We review the epidemiological literature on the possible impact of chemical and physical factors on pregnancy outcome. Effects of in-utero exposures on child health are not considered here. The highest levels of evidence concern the effects of passive smoking (on fetal growth), of lead (pregnancy-induced hypertension, fetal growth), of some Polychlorinated Biphenyls (PCB; on fetal growth) and, to a lesser extent, of atmospheric pollutants (on fetal growth and preterm delivery). For the other compounds, in particular non-persistent chemicals, the literature, which is generally based on poor exposure assessment, is less informative. In conclusion, the last decades have witnessed the development of mother-child cohorts in which exposure biomarkers have been assayed, allowing a large number of publications. For some persistent compounds, for which efficient exposure assessment approaches have been used, the literature indicates a likely impact on pregnancy outcomes. With the exception of air pollutants, the literature on non-persistent compounds is little conclusive; the assay of exposure biomarkers in repeated biological samples collected at relevant time points could help further increase knowledge regarding any health impact.
https://hal.archives-ouvertes.fr/hal-00916684

hal-00916684
https://hal.archives-ouvertes.fr/hal-00916684
https://hal.archives-ouvertes.fr/hal-00916684/document
DOI : 10.1016/j.jgyn.2013.02.012

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Maternal affective disorders are frequently treated with selective serotonin reuptake inhibitor medications (SSRIs); with up to 10% of women being prescribed these medications during pregnancy. Infant development depends on the early serotonergic environment, which is altered by perinatal SSRIs, raising concern about how these medications affect neural outcomes. While clinical and preclinical research suggests an impact of SSRIs on the developing brain, more research is needed to determine the effects on neuroplasticity, the serotonergic system, and the hypothalamic-pituitary-adrenal axis in neural regions mediating behavior. The current work investigated the effects of the SSRI, fluoxetine, on the serotonergic system in the prefrontal cortex (PFC) during pre-adolescence, and changes to synaptic markers and glucocorticoid receptor density in the cingulate cortex (medial PFC) of pre-adolescent and adult Sprague-Dawley male and female rats. To model aspects of Perinatal Depression and maternal anxiety, pre-gestational maternal stress was used resulting in male and female offspring from 4 groups: 1) control, 2) perinatal fluoxetine exposed, 3) pre-gestational maternal stress exposed, and 4) pre-gestational maternal stress + fluoxetine. Perinatal fluoxetine prevented the effects of maternal stress on 5-HT levels and 5-HT turnover ratio in the PFC of pre-adolescent offspring, particularly in females. However, pre-gestational stress reduced synaptophysin and PSD-95 densities in the cingulate cortex, effects that were more pronounced in males. Interestingly, perinatal fluoxetine exposure reduced GR density in adult males in this same brain area. Together, results show differential effects of perinatal SSRIs and pre-gestational maternal stress on neurodevelopment in the PFC of males and females.
ISSN: 0028-3908

hal-01647158
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01647158
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01647158/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01647158/file/Gemmel%20-%20Perinatal%20fluoxetine%20prevents%20the%20effect.pdf
DOI : 10.1016/j.neuropharm.2017.10.009

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Background Experimental evidence suggests that developmental exposure to persistent organic pollutants (POP) and to some non persistent pesticides may disrupt metabolic regulation of glucose metabolism and insulin secretion, and thereby contribute to the current epidemic of obesity and metabolic disorders. Quasi-experimental situations of undernutrition in utero have provided some information. However, the evidence in humans concerning the role of the prenatal environment in these disorders is contradictory, and little is known about long-term outcomes, such as type 2 diabetes, of prenatal exposure. Objectives Our aim was to evaluate the effects of prenatal exposure to POP and organophosphate pesticides on fetal markers of glucose metabolism in a sample of newborns from the Pelagie mother–child cohort in Brittany (France). Methods Dialkylphosphate (DAP) metabolites of organophosphate pesticides were measured in maternal urine collected at the beginning of pregnancy. Cord blood was assayed for polychlorinated biphenyl congener 153 (PCB153), p,p′-dichlorodiphenyl dichloroethene (DDE) and other POP. Insulin and adiponectin were determined in cord blood serum (n=268). Results A decrease in adiponectin and insulin levels was observed with increasing levels of DDE, but only in girls and not boys. Adiponectin levels were not related to the concentrations of other POP or DAP metabolites. Decreasing insulin levels were observed with increasing PCB153 concentrations. Insulin levels increased with DAP urinary levels. Additional adjustment for BMI z-score at birth modified some of these relations. Conclusions Our observations bring support for a potential role of organophosphate pesticides and POP in alterations to glucose metabolism observable at birth
ISSN: 0013-9351

hal-01259218
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01259218
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01259218/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01259218/file/Prenatal%20exposure%20to%20persistent%20organic%20pollutants%20and%20organophosphate%20pesticides%2C%20and%20markers%20of%20glucose%20metabolism%20at%20birth.pdf
DOI : 10.1016/j.envres.2016.01.005

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Mixtures of polybrominated diphenyl ethers (PBDEs) are present in indoor environments. Studies of the developmental effects of exposure to these chemicals in large prospective mother-child cohorts are required, with data on prenatal exposure and long-term follow-up of the children. We aimed to investigate the relationship between prenatal and childhood exposure to PBDEs and neurodevelopment at the age of six years. We determined the levels of PBDEs and other neurotoxicants in cord blood and dust collected from the homes of children for 246 families included in the PELAGIE mother-child cohort in France. We assessed two cognitive domains of the six-year-old children using the Wechsler Intelligence Scale for Children-IV. Verbal comprehension scores were lower in children from homes with higher concentrations of BDE99 (βDetects < median_vs_NonDetects = −1.6; 95% CI: −6.1, 2.9; βDetects≥median_vs_NonDetects = −5.4; −9.9, −1.0; ptrend = 0.02) and of BDE209 (β2nd_vs₁st_tertile = −1.8; 95% CI: −6.1, 2.5; β3rd_vs₁st_tertile = −3.2; −7.5, 1.2; ptrend = 0.15) in dust, particularly for boys (ptrend = 0.02 and 0.04, respectively). Working memory scores seemed to be lower in children with higher BDE99 concentrations in dust (ptrend = 0.10). No association was observed with cord blood levels of BDE209. Our findings are in agreement with those of four previous studies suggesting adverse cognitive outcomes among children associated with early-life exposure to penta-BDE mixtures, and provide new evidence for the potential neurotoxicity of BDE209. Several countries are in the process of banning the use of PBDE mixtures as flame-retardants. However, these compounds are likely to remain present in the environment for a long time to come
ISSN: 0161-813X

hal-01286255
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01286255
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01286255/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01286255/file/Childhood%20exposure%20to%20polybrominated%20diphenyl-accepted.pdf
DOI : 10.1016/j.neuro.2016.03.002

Éditeur(s) : HAL CCSD American Chemical Society
Résumé : International audience
The HIWATE (Health Impacts of long-term exposure to disinfection byproducts in drinking WATEr) project was a systematic analysis that combined the epidemiology on adverse pregnancy outcomes and other health effects with long-term exposure to low levels of drinking water disinfection byproducts (DBPs) in the European Union. The present study focused on the relationship of the occurrence and concentration of DBPs with in vitro mammalian cell toxicity. Eleven drinking water samples were collected from five European countries. Each sampling location corresponded with an epidemiological study for the HIWATE program. Over 90 DBPs were identified; the range in the number of DBPs and their levels reflected the diverse collection sites, different disinfection processes, and the different characteristics of the source waters. For each sampling site, chronic mammalian cell cytotoxicity correlated highly with the numbers of DBPs identified and the levels of DBP chemical classes. Although there was a clear difference in the genotoxic responses among the drinking waters, these data did not correlate as well with the chemical analyses. Thus, the agents responsible for the genomic DNA damage observed in the HIWATE samples may be due to unresolved associations of combinations of identified DBPs, unknown emerging DBPs that were not identified, or other toxic water contaminants. This study represents the first to integrate quantitative in vitro toxicological data with analytical chemistry and human epidemiologic outcomes for drinking water DBPs.
ISSN: 0013-936X

hal-00875923
https://hal.archives-ouvertes.fr/hal-00875923
DOI : 10.1021/es3024226
PUBMED : 22958121

Éditeur(s) : HAL CCSD Endocrine Society
Résumé : International audience
: Context:Masculinization depends on the fetal testis. Exposure of the human fetus during pregnancy to paracetamol or/and to other mild-analgesics is associated with an increased risk of cryptorchidism.Objective:We aimed at determining whether mild analgesics disrupted the morphology and endocrine function of the human testis.Design:We used an in vitro system based on the culture of human fetal testes exposed or not to paracetamol, its metabolite AM404, aspirin, indomethacin, ketoconazole at 10(-4) M to 10(-7) M.Setting:The study was conducted at the University of Rennes I.Patients/Participants:Human fetal testes were from pregnant women following induced abortion, between 7 and 12 weeks of gestation (GW).Main Outcome Measures:Testosterone (radioimmunoassay: RIA), Anti-Müllerian Hormone (AMH; ELISA), insulin-like factor 3 (INSL3; RIA), prostaglandin D2 and E2 (PGD2 and PGE2, respectively; ELISA), were assayed in the media. Testicular cells were counted using histology and image analysis. The possible nuclear receptor-mediated activities of the analgesics were investigated using reporter cell lines expressing estrogen (ERs), androgen (AR) and peroxysome proliferator-activated γ ( PPARγ) receptors.Results:Indomethacin and aspirin stimulated testosterone production, particularly by the younger testes (8-9 GW vs 10-12 GW). Paracetamol, AM404 and ketoconazole decreased INSL3 levels. Aspirin stimulated, whereas ketoconazole inhibited AMH production. PGE2 levels were inhibited by paracetamol, and aspirin in the 7-12 GW testes, and by indomethacin but only in 7-9.86 GW old testes. The inhibitory trends seen for PGD2 were not statistically significant.Conclusions:Analgesics at concentrations relevant to human exposure cause endocrine disturbances in the fetal testis. We suggest that the fetal human testis displays slight critical age windows for sensitivity to direct exposure to aspirin, indomethacin and paracetamol. The analgesic-induced inhibition of INSL3 may be the mechanism by which analgesics increase the risk of cryptorchidism. Greater caution is required concerning consumption of analgesics during pregnancy.
ISSN: 0021-972X

inserm-00876125
http://www.hal.inserm.fr/inserm-00876125
DOI : 10.1210/jc.2013-2531
PUBMED : 24030937

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
Background: Health care workers (HCWs) are occupationally exposed to various hazards, some associated with adverse pregnancy outcomes in previous reviews. This systematic review aims at synthesizing the recent literature on occupational exposures among HCWs related to fetal death, congenital anomalies, and fertility disorders. Methods: We searched the Medline database from 2000 to 2015 for articles about all potential occupational exposures of women and men working in this sector. Results: We retained 32 studies, most of them (n = 30) among women HCWs. Studies based on job title reported excess risks of some congenital anomalies (especially nervous and musculoskeletal systems) among HCWs compared to non-HCWs but no evidence about fetal death. Excess risks associated with specific exposures includes reports of some congenital anomalies forwomenexposed to anesthetic gases. Exposure to some sterilizing agents and, with less evidence, to antineoplastic drugs and to ionizing radiation, is associated with increased risks of miscarriage but not stillbirth. Strenuous work schedules appear to be associated with fertility disorders, but the evidence is limited. Only a few studies have been published since 2000 about non-ionizing radiation, or about fertility disorders related to chemical or physical agents, or about male HCWs. Conclusions: Despite the establishment of recommendations to limit exposures of HCWs, some excess risks of adverse pregnancy outcomes are still reported and need to be explained.
ISSN: 0271-3586

hal-01560148
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01560148
DOI : 10.1002/ajim.22711
PUBMED : 28514021

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Recent research has linked early life exposure to selective serotonin reuptake inhibitor medications (SSRIs) to modifications of social behaviors in children. Serotonin is a key regulator of neurodevelopment, social behaviors and mental health, and with the growing use of SSRIs to treat maternal affective disorders during the perinatal period, questions have been raised about the benefits and risks of perinatal SSRI exposure on the developing child. This review will highlight how perinatal SSRIs affect maternal care and neurodevelopmental outcomes related to social affiliative behaviors in offspring; such as play behaviors, social interactions, reproductive behaviors, and maternal care of the next generation. We will also review how early life exposure to SSRIs can alter related neurobiology, and the epigenome. Both clinical research and findings from animal models will be discussed. Understanding the impact of perinatal SSRIs on neurobehavioral outcomes will improve the health and well-being of subsequent generations.
ISSN: 0149-7634

hal-01619303
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01619303
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01619303/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01619303/file/Perinatal%20selective%20serotonin%20reuptake%20inhibitor%20medication_revised.pdf
DOI : 10.1016/j.neubiorev.2017.04.023

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
The seasonal patterns of conceptions and births differ between geographic areas. Several potential determinants of this variation have been identified, including biological, environmental and behavioral elements, but festive events are rarely mentioned. We investigated the possible association between the carnival and seasonal fertility variations in the French West Indies. We ran a retrospective registry-based study. The data were extracted from the registry of all births on Guadeloupe between 2000 and 2011 (n = 74,412), and from the Maternity Birth Register of the University Hospital, for all pregnancies of at least 14 completed weeks of gestation (observable conceptions) with an outcome recorded between 2007 and 2010 (n = 8,425). We compared data during and outside the carnival period for each year, including 2009, when there was no carnival due to a 44-day general strike. In all years other than 2009, the weekly number of births was higher for pregnancies initiated during the carnival period than for pregnancies initiated at other times, and the weekly number of observable conceptions was higher during the carnival period than at other times. Our findings support the hypothesis that carnivals in the French West Indies are associated with an increase in the number of conceptions and subsequent births.
ISSN: 1932-6203

hal-01485778
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01485778
DOI : 10.1371/journal.pone.0173102
PUBMED : 28253323

Éditeur(s) : HAL CCSD MDPI
Résumé : International audience
Infant and neonatal mortality indicators are known to vary geographically, possibly as a result of socioeconomic and environmental inequalities. To better understand how these factors contribute to spatial and temporal patterns, we conducted a French ecological study comparing two time periods between 2002 and 2009 for three (purposefully distinct) Metropolitan Areas (MAs) and the city of Paris, using the French census block of parental residence as the geographic unit of analysis. We identified areas of excess risk and assessed the role of neighborhood deprivation and average nitrogen dioxide concentrations using generalized additive models to generate maps smoothed on longitude and latitude. Comparison of the two time periods indicated that statistically significant areas of elevated infant and neonatal mortality shifted northwards for the city of Paris, are present only in the earlier time period for Lille MA, only in the later time period for Lyon MA, and decrease over time for Marseille MA. These city-specific geographic patterns in neonatal and infant mortality are largely explained by socioeconomic and environmental inequalities. Spatial analysis can be a useful tool for understanding how risk factors contribute to disparities in health outcomes ranging from infant mortality to infectious disease-a leading cause of infant mortality.
ISSN: 1660-4601

hal-01359563
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01359563
DOI : 10.3390/ijerph13060624
PUBMED : 27338439

Éditeur(s) : HAL CCSD
Résumé : International audience
Selective serotonin reuptake inhibitor medications (SSRIs) are the first lines of treatment for maternal affective disorders, and are prescribed to up to 10% of pregnant women. Concern has been raised about how perinatal exposure to these medications affect offspring neurobehavioral outcomes, particularly those related to social interactions, as recent research has reported conflicting results related to autism spectrum disorder (ASD) risk in children prenatally exposed to SSRIs. Therefore, the aim of this work was to investigate the effects of perinatal exposure to the SSRI fluoxetine on social play behaviors and the hypothalamic pituitary adrenal system, using a model of pre-gestational maternal stress. We also investigated synaptic proteins in the CA2, CA3, and dentate gyrus of the hippocampus, as well as number of immature neurons in the granule cell layer, as both measures of plasticity in the hippocampus have been linked to social behaviors. In pre-adolescent male and female Sprague-Dawley rat offspring, main findings show that perinatal fluoxetine prevents the negative effect of maternal stress on sibling play behavior. However, perinatal fluoxetine increased social aggressive play with a novel conspecific in both sexes and decreased time grooming a novel conspecific in males only. Perinatal fluoxetine also increased serum corticosteroid binding globulin levels, 5-HT levels in the hippocampus, and pre-synaptic density assessed via synaptophysin in the dentate gyrus. Social interaction was significantly correlated with changes in plasticity in the CA2 region of the hippocampus. Pre-gestational maternal stress exposure resulted in significantly decreased rates of hippocampal neurogenesis and synaptophysin density in the dentate gyrus of pre-adolescent males, but not females. Together, these results further characterize the role of perinatal SSRIs, maternal stress prior to conception, and sex/gender on developing social behaviors and related plasticity in the hippocampus of pre-adolescent offspring.
Psychoneuroendocrinology

hal-01579611
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01579611
DOI : 10.1016/j.psyneuen.2017.07.480
PUBMED : 28735226

Éditeur(s) : HAL CCSD
Résumé : International audience
BACKGROUND: Numerous studies have linked prenatal traffic-related air pollution exposure to fetal growth. Recently, several studies have suggested exploring this association independently among boys and girls because of potential sex-specific biological vulnerability to air pollution. Residence-based factors can also influence fetal growth by enhancing susceptibility to the toxic effects of air pollution and must also be considered in these relations. OBJECTIVE: We examined sex-specific associations between prenatal air pollution exposure and fetal growth and explored whether they differed by the urban-rural status of maternal residence. METHODS: This study relied on the PELAGIE mother-child cohort (2521 women, Brittany, France, 2002-2006). Fetal growth was assessed through birth weight, head circumference and small weight (SGA) and small head circumference (SHC) for gestational age. Nitrogen dioxide (NO2) concentrations at mothers' homes were estimated by using a land use regression model taking into account temporal variation during pregnancy. Associations between estimated NO2 concentrations and fetal growth were assessed with linear regression or logistic regression models, depending on the outcome investigated. RESULTS: An interquartile range (8.8µgm(-3)) increase in NO2 exposure estimates was associated with a 27.4g (95% CI 0.8 to 55.6) increase in birth weight and a 0.09cm (95% CI 0.00-0.17) significant increase in head circumference, among newborn boys only. Their risks of SGA and SHC were reduced (OR 0.70, 95% CI 0.53-0.92, OR 0.76, 95% CI 0.56-1.03, respectively, for an increase of 8.8µgm(-3)). No statistically significant trends were observed among girls. Urban-rural status modified the effect of air pollution only for SHC and again only for newborn boys. CONCLUSION: Findings from this study confirm the need to consider sex-specific associations between air pollution and fetal growth and to investigate possible mechanisms by which traffic-related air pollution may increase anthropometric parameters at birth
Environmental Research

hal-01205354
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01205354
DOI : 10.1016/j.envres.2015.09.006
PUBMED : 26378737