Exposure of pregnant women to organophosphate insecticides and child motor inhibition at the age of 10-12 years evaluated by fMRI.

BACKGROUND: Organophosphate pesticides (OP) are widely used for both agricultural and domestic purposes. Epidemiological studies suggest neurotoxicity in children after exposure to organophosphates pesticides (OP) at low levels but possible mechanism is still unclear. OBJECTIVES: We aimed at investigating the effects of prenatal exposure to OPs on inhibitory control of 10-12 year-old-children assessed by a motor inhibition task during functional magnetic resonance imaging (fMRI). METHODS: Ninety-five children from the PELAGIE cohort (Brittany-France, from 2002) underwent a fMRI examination during which inhibition was assessed by a Go/No-Go task. Task performance was assessed by average response latency, commission rate and composite performance score (PS). Whole brain activation was estimated by modeling the hemodynamic response related to inhibition demand and successful inhibition. OP exposure was assessed by measuring six dialkylphosphate (DAP) metabolites in the urine of women in early pregnancy (<19 WG). Concentrations were summed to obtain overall levels of diethylphosphate (DE), dimethylphosphate (DM) and total non-specific metabolites (DAP), standardized to homogenize sampling conditions and categorized into levels of exposure: low (reference), moderate or high. Regression models were adjusted for potential cofounders considered by restriction and statistical criteria. RESULTS: Moderate levels of DAP were associated with a decreased commission rate (ß = -6.65%, p = 0.04), indicating improved performance. Increasing levels of DM and DE were associated with decreased brain activity in the left inferior and bilateral superior frontal regions during successful inhibition. We did not observe any differential activation related to inhibitory demands. DISCUSSION: These results suggest that prenatal OPs may be associated with altered pattern of brain activity in regions related to inhibition among children and need to be confirmed by additional studies.

Exposure of pregnant women to persistent organic pollutants and cord sex hormone levels.

STUDY QUESTION: Is prenatal exposure to persistent organic pollutants (POPs) associated with variations of sex hormone levels in cord blood? SUMMARY ANSWER: Prenatal exposure to a number of POPs is associated with a disruption of hormone levels in cord blood, with sex specificities. WHAT IS KNOWN ALREADY: Epidemiological studies have reported disorders of reproductive health, in relation with POPs exposure during early life and the endocrine disruption properties of these chemicals have been suggested as possible mechanisms. STUDY DESIGN, SIZE, DURATION: A subset of 282 mother-child pairs was selected from the prospective population-based PELAGIE birth cohort (n = 3421, 2002-2006, Brittany, France). Pregnant women were recruited before 19 weeks of gestation and followed until delivery. PARTICIPANTS/MATERIALS, SETTING, METHODS: Sex hormone levels including sex hormone-binding globulin (SHBG), estradiol (E2), total testosterone (T), free testosterone (fT = T/SHBG) and the aromatase index (AI = T/E2) were measured in 282 cord blood samples. Anti-Müllerian hormone (AMH) was measured in male newborns only. Pesticide concentrations of α-endosulfan, ß-hexachlorocyclohexane (ß-HCH), γ-HCH, dieldrin, pp'-dichlorodiphenyldichloroethylene (p,p'-DDE), hexachlorobenzene (HCB), heptachlor epoxide (HCE), as well as PCBs (congeners 153, 187 and the sum of anti-estrogenic PCBs 118, 138, and 170) and decabrominated diphenyl ether (BDE209) were also measured in cord blood. Associations between sex hormones and POPs exposure were explored using multiple linear regressions adjusted for potential confounders. MAIN RESULTS AND THE ROLE OF CHANCE: High PCB levels were associated with an increase of SHBG (P-trend < 0.01) and AMH (P-trend < 0.05) and a decrease of fT (P-trend < 0.05) and AI (P-trend < 0.01). High pesticide levels, particularly α-endosulfan and HCE, were associated with an increase of SHBG (P < 0.05) and E2 (P < 0.01) and a decrease of fT (P < 0.05) and AI (P < 0.01). Several of these associations were stronger, or specific, among male or female newborns. The associations were not altered in the sensitivity analyses. LIMITATIONS, REASONS FOR CAUTION: The study population was of relatively small sample size, and some compounds rarely detected in cord blood. The high level of correlation between POPs makes it difficult to identify the most contributing POPs. Hormone measurements were performed at birth (in cord blood) and may not adequately represent the infant endocrine system. Multiple statistical testing may have led to false-positive associations. WIDER IMPLICATIONS OF THE FINDINGS: Our results are in discordance with those reported in the only published study of the kind but in accordance with studies about prenatal exposure to other endocrine disruptors such as phthalates. These findings may help understanding the pathways involved in adverse reproductive outcomes associated with POPs exposure. STUDY FUNDING/COMPETING INTERESTS: The PELAGIE cohort is funded by Inserm, French Ministry of Health, French Ministry of Labor, InVS, ANR, ANSES, and French Ministry of Ecology. None of the authors has any competing interest to declare.

Medical and sociodemographic risk factors for preterm birth in a French Caribbean population of African descent.

There appears to be an incompressible high rate of preterm births among populations of African origin irrespective of their geographic location. The objective of this study was to assess the risk factors for preterm birth in a French Caribbean population of African descent, offered medical care comparable to that on the French mainland, but presenting a higher rate of preterm birth. The study was based on a birth cohort at maternity hospitals in Guadeloupe (French West Indies) including 911 singleton pregnancies enrolled during their third trimester check-up visits. Associations between risk factors and the risk of preterm delivery (spontaneous and induced) were assessed using a multivariate Cox model. In addition, prevalences of sociodemographic and medical factors in Guadeloupe were compared with those on the French mainland. 144 women (15.8 %) delivered preterm, medically induced in 52 %. Women delivering preterm were more often over 35 years old (37 %), single (54 %), and had higher prevalence of prior preterm birth (20 %), prior miscarriage (37 %), lupus (3 %), asthma (14 %), gestational hypertension (26 %), gestational diabetes (13 %) and urinary tract infection (24 %) than women with term births. In the whole cohort, these risk factors were also more frequent than in mainland France. Our results suggest highly prevalent medical risk factors for preterm births in Guadeloupe. This observation combined with specific social risk factors (older maternal age, single living) less frequent on the French mainland probably explains a large part of a higher prevalence of preterm births in this population despite similar medical provision.

Maternal occupational exposure to solvents and congenital malformations: a prospective study in the general population.

OBJECTIVE: To study the relations between maternal occupational exposure to solvents during pregnancy and the risk of congenital malformations. METHODS: A prospective population-based cohort, specifically designed to study the impact of maternal exposure to solvents on the risk of congenital malformations, began in 2002 in three districts of Brittany (France). 3421 pregnant women were recruited until the end of 2005 by physicians before 19 weeks of gestation and followed through birth. Information on pregnancy outcomes was obtained from the hospital. Occupational exposure to solvents at the beginning of pregnancy was assessed from the women's self-reported occupational exposures at inclusion and from a job-exposure matrix (JEM). Sociodemographic characteristics, lifestyle factors, medical history, diseases during pregnancy were obtained at inclusion and from hospital records. Analyses were restricted to working women (n = 3005). Logistic regressions were used to adjust for potential confounders. RESULTS: 30.2% of the working women declared regular exposure to at least one product that may contain solvents. 21.3% of them were classified at least in the medium exposure category using the JEM. Occupations mainly classified as exposed by both assessment methods were hairdressers, nurses' aides, nurses and chemists/biologists. Significant associations were found between major congenital malformations and maternal occupational exposure to solvents, assessed by both self-report odds ratio (OR = 2.48, 95% CI 1.4 to 4.4 for regular exposure vs no exposure) and the JEM (OR = 3.48, 95% CI 1.4 to 8.4 for highest level of exposure vs no exposure). A significant dose-response trend was observed with both assessment methods. Several subgroups of major malformations were associated with maternal exposure to solvents (oral clefts, urinary malformations and male genital malformations). CONCLUSION: This study provides further evidence of an association between exposure to solvents during pregnancy and the risk of major malformations.

[Periconceptional folates and the prevention of orofacial clefts: role of dietary intakes in France]. / Folates en période péri-conceptionnelle et prévention du risque de fente orofaciale: rôle des apports alimentaires en France.

BACKGROUND: Orofacial clefts are among the most frequent congenital malformations at birth with a prevalence of 1 in 700 births in Europe. The implication of environmental factors in their etiology has been demonstrated. The role of folic acid, or folates, in the prevention of orofacial clefts is still debated although its efficacy has been demonstrated for the prevention of neural tube defects. METHODS: A case-control study was conducted in 7 hospitals in 4 centers in France. Cases (N=240) were children with non-syndromic orofacial cleft referred to one of the study hospitals for initial surgical repair in 1998 and 1999. Controls (N=236) matched for gender, geographic origin, and age were chosen in paediatric departments of the same hospitals. Usual dietary intake of folates was estimated using a food frequency questionnaire submitted to the mother at hospital. During the same interview, data on sociodemographic characteristics, medical and obstetrical history, tobacco and alcohol consumption, and vitamin supplements, were obtained. Odds ratios associated with quintiles of dietary intake of folates were estimated using logistic regression adjusting for known confounders. RESULTS: A significant dose-response relationship between the risk of orofacial clefts and a decrease in the intake of folates from diet was found, stronger for cleft palate without cleft lip. Only few women (<1%) declared having taken vitamin supplements containing folic acid when planning their pregnancy. CONCLUSION: Our study further suggests that folates are useful for the prevention of orofacial clefts during the periconceptual period. In our study, the estimated average daily intake of folates (270 microg/day) was below French national recommendations for the prevention of neural tube defects (400 microg/day). Since those insufficient folate intakes during the periconceptual period are not presently met by vitamin supplementation, the solution may come from the food fortification program proposed and implemented by the National Agency for Food Safety (AFSSA).

Parental exposure to polycyclic aromatic hydrocarbons and the risk of childhood brain tumors: The SEARCH International Childhood Brain Tumor Study.

Experimental evidence suggests that parental exposure to polycyclic aromatic hydrocarbons (PAH), which occurs primarily through tobacco smoke, occupational exposure, and air pollution, could increase the risk of cancer during childhood. Population-based case-control studies carried out in seven countries as part of the SEARCH Program compared data for 1,218 cases of childhood brain tumors and 2,223 controls (1976-1994). Parental occupational exposure to PAH during the 5-year period before birth was estimated with a job exposure matrix. Risk estimates were adjusted for child's age, sex, and study center. Paternal preconceptional occupational exposure to PAH was associated with increased risks of all childhood brain tumors (odds ratio (OR) = 1.3, 95% confidence interval: 1.1, 1.6) and astroglial tumors (OR = 1.4, 95% confidence interval: 1.1, 1.7). However, there was no trend of increasing risk with predicted level of exposure. Paternal smoking alone (OR = 1.4) was also associated with the risk of astroglial tumors in comparison with nonsmoking, non-occupationally-exposed fathers. Risks for paternal occupational exposure were higher, with (OR = 1.6) or without (OR = 1.7) smoking. Maternal occupational exposure to PAH before conception or during pregnancy was rare, and this exposure was not associated with any type of childhood brain tumor. This large study supports the hypothesis that paternal preconceptional exposure to PAH increases the risk of brain tumors in humans.

Chronic neck and shoulder pain, age, and working conditions: longitudinal results from a large random sample in France.

AIMS: To analyse the effects of age and occupational factors on both the incidence and the disappearance of chronic neck and shoulder pain after a five year follow up period. METHODS: A prospective longitudinal investigation (ESTEV) was carried out in 1990 and 1995 in seven regions of France. A random sample of male and female workers born in 1938, 1943, 1948, and 1953 was selected from the occupational physicians' files. In 1990, 21 378 subjects were interviewed (88% of those contacted), and 87% were interviewed again in 1995. Chronic neck and shoulder pain satisfying specific criteria, and psychosocial working conditions were investigated by a structured self administered questionnaire and a clinical examination. RESULTS: Prevalence (men 7.8%, women 14.8% in 1990) and incidence (men 7.3%, women 12.5% for the period 1990-95) of chronic neck and shoulder pain increased with age, and were more frequent among women than men in every birth cohort. The disappearance rate of chronic neck and shoulder pain decreased with age. Some adverse working conditions (repetitive work under time constraints, awkward work for men, repetitive work for women) contributed to the development of these disorders, independently of age. Psychosocial factors seemed to play a role in both the development and disappearance of chronic neck and shoulder pain. Data did not show specific interactions between age and working conditions. CONCLUSIONS: The aging of the workforce appears to contribute to the widespread concern about chronic neck and shoulder pain. A better understanding of work activity regulation of older workers can open up new preventive prospects.

Ecological analysis of digestive cancer mortality related to contamination by diarrhetic shellfish poisoning toxins along the coasts of France.

Shellfish consumers are exposed to the risk of diarrhea from, among other contaminants, algae that produce diarrhetic shellfish poisoning (DSP) toxins, such as Dinophysis spp. These illnesses have been effectively prevented since 1984, when a phycotoxin monitoring network was set up along the coasts of France. There is nonetheless concern that residual levels of okadaic acid, a known tumor promoter that is the main toxin present in French coastal waters, might increase the risk of cancer among regular shellfish consumers. To test this hypothesis, we conducted an ecological study linking digestive cancer mortality rates with a proxy measure of contamination by DSP toxins in 59 coastal areas. Observed and expected numbers of deaths (using national rates as the reference) were computed by sex, cause of death, and area for two time periods: 1984-1988 and 1989-1993. The level of contamination in each area was estimated by the total number of weeks since monitoring began that production was shut down because of DSP toxin contamination. Using both Poisson regressions and test for trends of standardized mortality ratios across four exposure categories, we found some evidence of associations for several digestive cancer sites (esophagus, stomach, colon, liver, and total digestive cancers for men; stomach and pancreatic cancers for women). Among men, the only statistically significant result that remained after taking possible confounding by alcohol use into account involved colon cancer. The conclusions provided by this analysis are very tentative; they need to be reproduced and interpreted in the light of additional information on the potential long-term effects of DSP toxins. In the absence of human data, they provide some indication of a possible association between exposure to DSP toxins and digestive cancers.

Social prognostic factors of mortality in a random cohort of Geneva subjects followed up for a period of 12 years.

STUDY OBJECTIVE: To analyse the relative risk (RR) of mortality related to social factors independent of health status and occupational category. SETTING: Subjects were Swiss men and women aged 40-65 years. DESIGN: A random sample of 820 people living in Geneva were followed up prospectively between 1984 and 1996. The social, occupational, and health data were gathered at subjects' homes in 1984 using a standardised questionnaire. Information about deaths and the corresponding dates were obtained from updated files of the Swiss Federal Office of Statistics (OFS). Risk of mortality was examined according to a Cox model. MAIN RESULTS: There were several social prognostic factors of mortality with relative risks greater than 3.0 (RR > 3.0) independent of health and occupational status. These factors were: a period of unemployment during life time, the feeling of not demonstrating initiative in the occupational setting, and not having participated in social activities. CONCLUSION: The results suggest that differential mortality determined by occupational status can be explained in part by factors that are characteristic of "life style", social dynamics, occupational context, and ruptures during the course of occupational life.

Risk factors of early menopause in two generations of gainfully employed French women.

OBJECTIVES: Numerous studies have been focused on the detection of factors which can act on the age of menopause. Little is known about the factors related to the occurrence of an early menopause. Some factors such as occupational work factors and generational effects have not been taken into account as yet. METHODS: We examined the risk factors of early natural menopause (before age 45) in a large random sample of gainfully employed French women born in the years 1938 (n = 1743) and 1943 (n = 1959). The subjects were selected from files of an occupational physician. A woman was considered to be post-menopausal when at least 12 consecutive months had passed without menstruation at the time of the survey. Subjects were questioned and examined during their annual visit by the occupational physician. Occupational history, working conditions, living conditions, smoking habits and reproductive history were explored. RESULTS: The prevalence of early natural menopause, before age 45, was higher in the generation of 1938 (5.3%) than in that of 1943 (3.3%) with P < 0.01. After multivariate regressions, significant relationships existed statistically between the occurrence of early natural menopause and marital status, educational level, age at first childbirth and breast-feeding of children. CONCLUSIONS: Our results show important generation effects. There was no evidence of a significant relationship between early natural menopause at 45 years of age and factors relative to heavy physical work conditions.

[Predictive factors of physical disability in a cohort of retired persons in Paris followed during 10 years]. / Facteurs prédictifs d'incapacité physique dans une cohorte de retraités parisiens suivis pendant dix ans.

OBJECTIVE: The objective of the present study was to examine predictors of physical disability in a survey of retired men and women living in the Paris area followed-up longitudinally for 10 years. METHODS: Subjects were randomly selected in a supplementary retirement pension fund. In all 627 subjects took part in the first phase of the survey (1982-83) and 392 in the follow-up phase (1992-93). At the 10-year follow-up, there were 185 confirmed deaths and 50 subjects refused to participate or could not be traced. Physical disability was measured by difficulties reported by the subjects for seven basic activities of daily life. Possible predictors, socio-demographic, impairments, physical activities, working conditions during working life were explored at T1. RESULTS: The incidence of physical disability was 41.4% for men and 57.6% for women. For disability in mobility, the incidence was 37.1% for men and 54.7% for women. In multivariate analysis, predictors of physical disability were social category (clerks), no physical activities, use of medicine, mental impairment. The predictors of disability in mobility were sex (women), social category (clerks), use of medicine, cardio-respiratory and sensory impairments. On the contrary, subjects with mental impairment had a lower incidence of disability in mobility than subjects without mental impairment. CONCLUSION: The results confirm the two poles of disability: biomedical and social. Working conditions during working life do not seem to play a direct part in incidence of disability at ten years follow-up.

[Age, work and spinal pain]. / Age, travail et douleurs rachidiennes.

BACKGROUND: To examine whether the relationship between age and musculoskeletal disorders in the spine is specific to one localization (cervical, dorsal, lumbar) or due to the accumulation of lesions with age. METHODS: Data were gathered from the ESTEV study among a randomly selected sample of 21,378 French workers, followed by 390 occupational physicians during the year 1990. The subjects, males or females, were born in 1938, 1943, 1948, 1953. Participation rate (88%) did not depend on age and sex. Data were collected during annual medical examination for medical variables, and using standardized self questionnaires for occupational exposures and work constraints for actual or past jobs. RESULTS: Data on musculo-skeletal disorders, defined as pains during the last 6 months before examination, were recorded by occupational physician. Each painful localization was associated with the main factors described in the literature, particularly heavy physical work factors and psycho-social factors of work. There was no interaction between age and any of these. At the opposite, in male as female subjects, there was a statistically significant interaction between age, multiple exposures to heavy physical work factors and the frequency of multiple localizations of pain in the spine. CONCLUSION: Results suggest that accumulation of pain in the different localizations of the spine might account for accelerated aging process of the musculo-skeletal structure of the spine which can reflect effects of environmental work factors.

Spatial variation of natural radiation and childhood leukaemia incidence in Great Britain.

This paper describes an analysis of the geographical variation of childhood leukaemia incidence in Great Britain over a 15 year period in relation to natural radiation (gamma and radon). Data at the level of the 459 district level local authorities in England, Wales and regional districts in Scotland are analysed in two complementary ways: first, by Poisson regressions with the inclusion of environmental covariates and a smooth spatial structure; secondly, by a hierarchical Bayesian model in which extra-Poisson variability is modelled explicitly in terms of spatial and non-spatial components. From this analysis, we deduce a strong indication that a main part of the variability is accounted for by a local neighbourhood 'clustering' structure. This structure is furthermore relatively stable over the 15 year period for the lymphocytic leukaemias which make up the majority of observed cases. We found no evidence of a positive association of childhood leukaemia incidence with outdoor or indoor gamma radiation levels. There is no consistent evidence of any association with radon levels. Indeed, in the Poisson regressions, a significant positive association was only observed for one 5-year period, a result which is not compatible with a stable environmental effect. Moreover, this positive association became clearly non-significant when over-dispersion relative to the Poisson distribution was taken into account.

[Relationship between perceived health status and career choice in a sample of wage-earners]. / Relations entre les caractéristiques de la santé perçue et le choix de la profession dans un échantillon de salariés.

Many factors were related with subjective health status (SHS), but few studies have focused on identifying some intrinsic personal factors like the choice of job and perceived working situations. The present paper examines the relationships among such factors in a large French sample. Data were collected from 21,378 subjects who were randomly selected from the lists of male and female wage earners who were followed up by 380 occupational physicians and who were born in 1938, 1943, 1948 or 1953. SHS was evaluated using the French version of the Nottingham Health Profile (NHP). Socio-demographic and job characteristics were assessed by means of closed questions during the annual medical examination. Results showed that low subjective health status was related to sex, age and perceived working situation: for each of the six areas of the NHP (pain, physical mobility, energy, sleep, social isolation, emotional reactions) there was a lower SHS for women and a decrease with age for both sexes. The poorer the perceived working situations the worse was the SHS. Using general linear models it appeared that independently of these factors and the socio-economical category dichotomized in upper classes versus lower classes, those who had claimed to have not chosen their job had a lower SHS, whatever the area of SHS. Awaiting the second survey in 1995, it is difficult to explain these results from this cross sectional analysis: is the choice of job a possible risk factor or an artefact due to some unmeasured confounding factors like motivation or job satisfaction.

Evolution of osteoarticular disorders as a function of past heavy physical work factors: longitudinal analysis of 627 retired subjects living in the Paris area.

The relations between osteoarticular disorders and occupational exposure to heavy physical work factors were studied in a random sample of retired subjects living in the Paris area, all of whom had contributed to the same retirement pension fund. 627 subjects were originally seen in 1982-3 and 464 of them were seen again five years later. On both occasions, the same questionnaire was completed during a home interview. Osteoarticular disorders were evaluated by the presence of pain, with or without restricted joint movement, for at least six months before interview. The heavy physical work factors were those reported by the subject at the first interview, and only subjects who stated that they had been exposed to these factors for more than 10 years were considered as exposed persons. For those who were seen twice, the frequency of osteoarticular pain increased during the five years between the two interviews, from 52% to 65% in the men and 72% to 82% in the women. Among both sexes, these frequencies were significantly higher in those who stated that in the past they had to carry heavy weights and work in tiring positions. The increases in frequency of pain during the five year study period were also related to these occupational factors. In general, the frequencies for subjects not exposed to occupational factors caught up with those found for the exposed group. This interaction of age with the relation between exposure to heavy physical work factors and osteoarticular disorders does not seem to be explained by confounding factors, including age at the first interview, the fact of living alone, of being a former manual worker, of having a cardiorespiratory disorder, and smoking habits. The results of the survey suggest that working conditions are an important cause of osteoarticular disorders that last well beyond the end of working life.