Éditeur(s) : HAL CCSD
Résumé : International audience
BACKGROUND: Several studies suggest that exposure to organophosphate insecticides (OP) during pregnancy impairs neurodevelopment in children. OBJECTIVES: We evaluated associations between biomarkers of prenatal and postnatal OP exposure and cognitive function of 6-year-olds in a French longitudinal birth cohort. METHODS: In 2002-2006, the PELAGIE mother-child cohort enrolled pregnant women from Brittany. For a random subcohort, we measured nonspecific dialkylphosphate metabolites (DAP) of OP in one maternal urine sample, collected before 19 weeks' gestation, and in one urine sample collected from their 6-year-old children. Six subtests of the Wechsler Intelligence Scale for Children-4th edition (WISC-IV) was administered at 6 years to evaluate cognitive function (n=231). Linear regression models controlling for factors including maternal intelligence and the Home Observation for Measurement of the Environment score were used. RESULTS: WISC-IV scores were not significantly associated with prenatal or childhood total DAP metabolites. WISC verbal comprehension score was significantly higher in association with the highest maternal urinary concentrations of diethylphosphate metabolites (DE) (5.5; 95% CI: 0.8, 10.3 for extgreater 13.2 nmol/L versus extlessLOQ), while WISC working memory score was significantly lower in association with the highest urinary concentrations of DE metabolites at age 6 years (-3.6; 95% CI: -7.8, -0.6 for extgreater 11.1 nmol/L versus extlessLOD). CONCLUSION: This study found no evidence that prenatal OP exposure adversely affected cognitive function in 6-year-olds, perhaps because of the higher population's socioeconomic status than in previous studies though other causal and non-causal explanations are also possible. The negative association between WISC score and concurrent DE urinary concentrations requires replication by longitudinal studies investigating childhood OP exposure
Environmental Health Perspectives

hal-01207282
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01207282
DOI : 10.1289/ehp.1409472
PUBMED : 26394442

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 Public Library of Science
Résumé : International audience
BACKGROUND: The use of pesticides and the related environmental contaminations can lead to human exposure to various molecules. In early-life, such exposures could be responsible for adverse developmental effects. However, human health risks associated with exposure to complex mixtures are currently under-explored. OBJECTIVE: THIS PROJECT AIMS AT ANSWERING THE FOLLOWING QUESTIONS: What is the influence of exposures to multiple pesticides on the metabolome? What mechanistic pathways could be involved in the metabolic changes observed? METHODS: Based on the PELAGIE cohort (Brittany, France), 83 pregnant women who provided a urine sample in early pregnancy, were classified in 3 groups according to the surface of land dedicated to agricultural cereal activities in their town of residence. Nuclear magnetic resonance-based metabolomics analyses were performed on urine samples. Partial Least Squares Regression-Discriminant Analysis (PLS-DA) and polytomous regressions were used to separate the urinary metabolic profiles from the 3 exposure groups after adjusting for potential confounders. RESULTS: The 3 groups of exposure were correctly separated with a PLS-DA model after implementing an orthogonal signal correction with pareto standardizations (R2 = 90.7% and Q2 = 0.53). After adjusting for maternal age, parity, body mass index and smoking habits, the most statistically significant changes were observed for glycine, threonine, lactate and glycerophosphocholine (upward trend), and for citrate (downward trend). CONCLUSION: This work suggests that an exposure to complex pesticide mixtures induces modifications of metabolic fingerprints. It can be hypothesized from identified discriminating metabolites that the pesticide mixtures could increase oxidative stress and disturb energy metabolism.
ISSN: 1932-6203

inserm-00863407
http://www.hal.inserm.fr/inserm-00863407
http://www.hal.inserm.fr/inserm-00863407/document
http://www.hal.inserm.fr/inserm-00863407/file/journal.pone.0064433.pdf
PUBMED : 23704985

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Pyrethroids are insecticides frequently used in agriculture and in the home; exposure occurs through dietary and non-dietary pathways, including indoor and outdoor environmental contamination. Our objective was to study the potential determinants of pyrethroid metabolite concentrations measured in children's urine samples and in the dust of their homes. Specifically, we measured urinary metabolites from morning spot samples of 245 six-year- old children living in Brittany (France) in 2009-2012 and from dust vacuumed from the floor of their homes. Mothers reported home insecticide use, dietary habits, sociodemographic data; residential and school proximity to agricultural crops was assessed with spatialized data. The metabolites cis-DBCA, trans-DCCA, cisDCCA, 3-PBA, and F-PBA were detected in 84, 95, 64, 63, and 16% of the urine samples, respectively. Permethrin, cypermethrin, cyfluthrin, deltamethrin, and tetramethrin pyrethroids were detected in 100, 56, 9, 15, and 26% of the dust samples, respectively. Multiple regression analysis suggested diet plays a role in children's exposure, in particular, the food groups "pasta, rice or semolina" (for cis-DCCA and F-PBA), fruit (3-PBA), "breakfast cereals and whole grain bread" (cis-DBCA), and the global proportion of organic food in diet (for cis-DBCA, trans-DCCA). Children with a parent occupationally exposed to pesticides were about 3-times more likely to have higher urinary concentrations of 3-PBA (OR = 2.8, 95% CI [1.2; 6.5]). Dust content was correlated mainly with household insecticide use: higher mean concentrations of permethrin (beta = 0.8 [0.3; 1.3], in mu g/g) and an increased risk of a detectable level of cyfluthrin (OR = 4.7 [1.7; 12.9]) were observed in home dust, for indoor use of at least twice a year. Outdoor insecticide use at least once a year was associated with detection in dust of cypermethrin (OR = 3.0 [1.3; 6.7]) and tetramethrin (OR = 3.7 [1.6; 8.3]). Three positive and one negative correlations (out of 11) between urinary metabolite concentrations and home dust contents of their possible corresponding parent compounds were observed. The strength of this study lies in its concurrent use of biomarkers, environmental measurements, and potential sources of exposure. Its limitations include the use of a single urine sample and imprecise data about pyrethroid use in local agriculture.
ISSN: 0160-4120

hal-01560147
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01560147
DOI : 10.1016/j.envint.2017.04.007
PUBMED : 28453973

Éditeur(s) : HAL CCSD Lippincott, Williams & Wilkins
Résumé : International audience
BACKGROUND: People in developed countries are widely exposed to low levels of organochlorine pesticides, polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs). Seafood is a major contributor to PCB exposure. Toxicity of those various pollutants to reproductive and endocrine functions raises questions about possible effects on fertility. We explored whether serum levels of these pollutants and seafood consumption were associated with the fertility of couples enrolled in a French birth cohort (PELAGIE). METHODS: Time-to-pregnancy was investigated in 3,421 pregnant women by asking how many months they had taken to conceive. Levels of 14 organochlorine pesticides, 12 PCBs, and 10 PBDE compounds were measured in cord blood serum from a random subcohort (n = 394). Mercury concentrations measured in maternal hair were considered as a potential coexposure. Fecundability odds ratios (ORs) were estimated from multivariate discrete-time Cox proportional hazard models. RESULTS: Shellfish consumption was associated with longer time-to-pregnancy (fecundability OR ≥twice/week vs. 0.410 µg/L vs. <0.266 µg/L, fecundability OR = 0.46 [0.32-0.66]). In multiple sensitivity analyses, reduced fecundability was most consistently associated with shellfish consumption, p,p'-DDE, total PCBs, PCB153, and PCB187. Models that simultaneously included multiple coexposure factors led to similar conclusions. CONCLUSIONS: Our findings were robust in sensitivity analyses, including analysis restricted to primiparous women. These results suggest that PCBs, p,p'-DDE, and other shellfish contaminants may impair human fertility.
ISSN: 1044-3983

inserm-00826533
http://www.hal.inserm.fr/inserm-00826533
DOI : 10.1097/EDE.0b013e31827f53ec
PUBMED : 23348067

Éditeur(s) : HAL CCSD
Résumé : International audience
Reply: We thank Keelan and colleagues for their letter questioning the accuracy of testosterone measurement in cord blood obtained by immunoassay methods...
Human Reproduction

hal-01560277
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01560277
DOI : 10.1093/humrep/dex076
PUBMED : 28453619

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Perinatal exposure to endocrine-disrupting chemicals may affect thyroid hormones homeostasis and impair brain development. Chlordecone, an organochlorine insecticide widely used in the French West Indies has known estrogenic and progestin properties, but no data is available, human or animal, on its action on thyroid hormone system. Our aim was to evaluate the impact of perinatal exposure to chlordecone on the thyroid hormone system of a sample of infants from the Timoun mother-child cohort in Guadeloupe and their further neurodevelopment. Chlordecone was measured in cord blood and breast milk samples. Thyroid stimulating hormone (TSH), free tri-iodothyronine (FT3), free thyroxine (FT4) were determined in child blood at 3 months (n=111). Toddlers were further assessed at 18 months using an adapted version of the Ages and Stages Questionnaire (ASQ). Cord chlordecone was associated with an increase in TSH in boys, whereas postnatal exposure was associated with a decrease in FT3 overall, and in FT4 among girls. Higher TSH level at 3 months was positively associated with the ASQ score of fine motor development at 18 months among boys, but TSH did not modify the association between prenatal chlordecone exposure and poorer ASQ fine motor score. Perinatal exposure to chlordecone may affect TSH and thyroid hormone levels at 3 months, differently according to the sex of the infant. This disruption however did not appear to intervene in the pathway between prenatal chlordecone exposure and fine motor child development.
ISSN: 0013-9351

hal-01134317
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01134317
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01134317/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01134317/file/Perinatal%20exposure%20to%20chlordecone_accepted.pdf
PUBMED : 25747818

Éditeur(s) : HAL CCSD BMJ Publishing Group
Résumé : International audience
Objective The potential impact of environmental exposure to pyrethroid insecticides on child neurodevelopment has only just started to receive attention despite their widespread use. We investigated the associations between prenatal and childhood exposure to pyrethroid insecticides and behavioural skills in 6-year-olds. Methods The PELAGIE cohort enrolled 3421 pregnant women from Brittany, France between 2002 and 2006. 428 mothers were randomly selected for the study when their children turned 6, and 287 (67%) agreed to participate. Children's behaviour was assessed using the Strengths and Difficulties Questionnaire (SDQ). Three subscales (prosocial behaviour, internalising disorders and externalising disorders) were considered. Five pyrethroid metabolites were measured in maternal and child urine samples collected between 6 and 19 gestational weeks and at 6 years of age, respectively. Logistic regression and reverse-scale Cox regression models were used to estimate the associations between SDQ scores and urinary pyrethroid metabolite concentrations, adjusting for organophosphate metabolite concentrations and potential confounders. Results Increased prenatal cis-3-(2,2-dichlorovinyl)-2,2dimethylcyclopropane carboxylic acid (DCCA) concentrations were associated with internalising difficulties (Cox p value=0.05). For childhood 3phenoxybenzoic acid (PBA) concentrations, a positive association was observed with externalising difficulties (Cox p value=0.04) and high ORs were found for abnormal or borderline social behaviour (OR 2.93, 95% CI 1.27 to 6.78, and OR 1.91, 95% CI 0.80 to 4.57, for the intermediate and highest metabolite categories, respectively). High childhood trans-DCCA concentrations were associated with reduced externalising disorders (Cox p value=0.03). Conclusions The present study suggests that exposure to certain pyrethroids, at environmental levels, may negatively affect neurobehavioral development by 6 years of age.
ISSN: 1351-0711

hal-01519255
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01519255
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01519255/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01519255/file/Behavioural%20disorders%20in%206-year-old%20children_JFViel_HAL.pdf
DOI : 10.1136/oemed-2016-104035

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 National Institute of Environmental Health Sciences
Résumé : International audience
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) [beta (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) [beta (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.
ISSN: 0091-6765

hal-01519256
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01519256
DOI : 10.1289/EHP39
PUBMED : 27740510

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Pyrethroid insecticides are widely used in agriculture and in homes. Despite the neurotoxicity of these insecticides at high doses, few studies have examined whether lower-level exposures could adversely affect children's neurodevelopment. The PELAGIE cohort included 3421 pregnant women from Brittany, France between 2002 and 2006. When their children reached their sixth birthday, 428 mothers from the cohort were randomly selected, successfully contacted and found eligible. A total of 287 (67%) mothers agreed to participate with their children in the neuropsychological follow-up. Two cognitive domains were assessed by the Wechsler Intelligence Scale for Children: verbal comprehension and working memory. Five pyrethroid and two organophosphate insecticide metabolites were measured in maternal and child first-void urine samples collected between 6 and 19 gestational weeks and at 6 years of age, respectively. Linear regression models were used to estimate associations between cognitive scores and urinary pyrethroid metabolite concentrations, adjusting for organophosphate metabolite concentrations and potential confounders. Maternal prenatal pyrethroid metabolite concentrations were not consistently associated with any children's cognitive scores. By contrast, childhood 3-PBA and cis-DBCA concentrations were both negatively associated with verbal comprehension scores (P-trend = 0.04 and P-trend < 0.01, respectively) and with working memory scores (P-trend = 0.05 and P-trend < 0.01, respectively). No associations were observed for the three other childhood pyrethroid metabolite concentrations (4-F-3-PBA, cis-DCCA, and trans-DCCA). Low-level childhood exposures to deltamethrin (as cis-DBCA is its principal and selective metabolite), in particular, and to pyrethroid insecticides, in general (as reflected in levels of the 3-PBA metabolite) may negatively affect neurocognitive development by 6 years of age. Whatever their etiology, these cognitive deficits may be of importance educationally, because cognitive impairments in children interfere with learning and social development. Potential causes that can be prevented are of paramount public health importance
ISSN: 0160-4120

hal-01162374
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01162374
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01162374/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01162374/file/Pyrethroid%20insecticide%20exposure.pdf
DOI : 10.1016/j.envint.2015.05.009

Éditeur(s) : HAL CCSD National Institute of Environmental Health Sciences
Résumé : International audience
BACKGROUND: Glycol ethers are present in a wide range of occupational and domestic products. Animal studies have suggested that some of them may affect ovarian function. OBJECTIVE: To study the relation between women's exposure to glycol ethers and time to pregnancy. METHODS: Urine from randomly selected women in the PELAGIE mother-child cohort who had samples collected before 19 weeks of gestation was tested to measure eight glycol ether metabolites by chromatography coupled to mass spectrometry. Time to pregnancy was collected at the beginning of the pregnancy by asking women how many months they took to conceive. Associations between metabolite levels and time to pregnancy were estimated in 519 women with complete data using discrete-time Cox proportional hazards models to adjust for potential confounders. RESULTS: Glycol ether metabolites were detected in 6% (for ethoxyacetic acid) to 93% (for phenoxyacetic and butoxyacetic acids) of urine samples. Phenoxyacetic acid was the only metabolite with a statistically significant association with longer time to pregnancy (fecundability OR 0.82; 95% CI: 0.63, 1.06 for the second and third quartile combined; fecundability OR 0.70; 95% CI: 0.52, 0.95 for a fourth-quartile (≥1.38 mg/L) vs. first-quartile concentration (<0.14 mg/L)). This association remained stable after multiple sensitivity analyses. CONCLUSION: Phenoxyacetic acid, which was present in most of the urine samples tested in our study, was associated with increased time to pregnancy. This metabolite and its main parent compound, 2-phenoxyethanol, are plausible causes of decreased fecundability, but may also be surrogates for potential co-exposures frequently present in cosmetics.
ISSN: 0091-6765

hal-00866023
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00866023
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00866023/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00866023/file/Urinary_Glycol_Ether-accepted.pdf
DOI : 10.1289/ehp.1206103