Early exposure to mercury and cardiovascular function of seven-year old children in Guadeloupe (French West Indies).

BACKGROUND: The cardiotoxicity of prenatal exposure to mercury has been suggested in populations having regular contaminated seafood intake, though replications in the literature are inconsistent. METHODS: The Timoun Mother-Child Cohort Study was set up in Guadeloupe, an island in the Caribbean Sea where seafood consumption is regular. At seven years of age, 592 children underwent a medical examination, including cardiac function assessment. Blood pressure (BP) was taken using an automated blood pressure monitor, heart rate variability (HRV, 9 parameters) and electrocardiogram (ECG) characteristics (QT, T-wave parameters) were measured using Holter cardiac monitoring during the examination. Total mercury concentrations were measured in cord blood at birth (median = 6.6 µg/L, N = 399) and in the children's blood at age 7 (median = 1.7 µg/L, N = 310). Adjusted linear and non-linear modelling was used to study the association of each cardiac parameter with prenatal and childhood exposures. Sensitivity analyses included co-exposures to lead and cadmium, adjustment for maternal seafood consumption, selenium and polyunsaturated fatty acids (n3-PUFAs), and for sporting activity. RESULTS: Higher prenatal mercury was associated with higher systolic BP at 7 years of age (ßlog2 = 1.02; 95% Confidence Interval (CI) = 0.10, 1.19). In boys, intermediate prenatal exposure was associated with reduced overall HRV and parasympathetic activity, and longer QT was observed with increasing prenatal mercury (ßlog2 = 4.02; CI = 0.48, 7.56). In girls, HRV tended to increase linearly with prenatal exposure, and no association was observed with QT-wave related parameters. Mercury exposure at 7 years was associated with decreased BP in girls (ßlog2 = -1.13; CI = -2.22, -0.004 for diastolic BP). In boys, the low/high-frequency (LF/HF) ratio increased for intermediate levels of exposure. CONCLUSION: Our study suggests sex-specific and non-monotonic modifications in some cardiac health parameters following prenatal exposure to mercury in pre-pubertal children from an insular fish-consuming population.

Occupational exposure to organic solvents during pregnancy and child behavior from early childhood to adolescence.

BACKGROUND: Organic solvents are used in formulating an extensive range of products for professional use. Animal and human studies suggest that in utero solvent exposure may affect neurodevelopment. Our objective was to assess the association between occupational exposure to solvents during pregnancy and child behavior aged 2-12 years. METHODS: The French mother-child cohort PELAGIE (2002-2006) included 3,421 women recruited in early pregnancy. Occupational exposure to solvents was self-reported. For 459 children, parents used a questionnaire derived from the Child Behavior Checklist and the Preschool Social Behavior Questionnaire to assess their child's behavior, at age 2, and the Strengths and Difficulties Questionnaire at ages 6 and 12. A cross-lagged structural equation modeling approach was used to assess direct and indirect associations between exposure and child behavior. RESULTS: At age 2, an increased externalizing behavior score was suggested with prenatal exposure to solvents (mean change in standardized score (95%CI): 0.28 (-0.01, 0.57) for occasional exposure and 0.23 (-0.05, 0.51) for regular exposure). At ages 6 and 12, distinct sex-specific patterns were observed: among boys, no association with externalizing behavior was observed, while among girls, an association was seen for both occasional and regular exposure (total effect at age 12: 0.45 (0.06,0.83) and 0.40 (0.03, 0.76), respectively). For both sexes, occasional exposure may be associated with internalizing behavior at ages 6 and 12 (total effect at age 6: 0.37 (0.06, 0.68) and at age 12: 0.27 (-0.08, 0.62)). CONCLUSIONS: Occupational exposure to solvents during pregnancy may impact child behavior through either direct or cumulative effects during childhood; these associations may persist until early adolescence, especially among girls.

Heavy metals and diminished ovarian reserve: single-exposure and mixture analyses amongst women consulting in French fertility centres.

RESEARCH QUESTION: Do heavy metals affect the risk of diminished ovarian reserve (DOR) in women of reproductive age? DESIGN: A total of 139 cases and 153 controls were included between 2016 and 2020. The participants were aged between 18 and 40 years and attended consultations for couple infertility in one of four fertility centres in western France. Cases of DOR were defined as women with an antral follicle count less than 7, anti-Müllerian hormone levels 1.1 ng/ml or less, or both. Controls were frequency matched on age groups and centres, and were women with normal ovarian reserve evaluations, no malformations and menstrual cycles between 26 and 35 days. Heavy metals (lead, mercury, cadmium and chromium) were measured in whole blood at inclusion. Single-exposure associations were examined with multivariable logistic regressions adjusted on potential confounders. Mixture effects were investigated with quantile g-computation and Bayesian kernel machine regression (BKMR). RESULTS: Chromium as a continuous exposure was significantly associated with DOR in unadjusted models (OR 2.07, 95% CI 1.04 to 4.13) but the association was no longer significant when confounders were controlled for (adjusted OR 2.75, 95% CI 0.88 to 8.60). Similarly, a statistically significant association was observed for the unadjusted second tercile of cadmium exposure (OR 1.87, 95% CI 1.06 to 3.30); however, this association was no longer statistically significant after adjustment. None of the other associations tested were statistically significant. Quantile g-computation and BKMR both yielded no significant change of risk of DOR for the mixture of metals, with no evidence of interaction. CONCLUSIONS: Weak signals that some heavy metals could be associated with DOR were detected. These findings should be replicated in other studies.

Prenatal and childhood exposure to ambient air pollution and cognitive function in school-age children: Examining sensitive windows and sex-specific associations.

BACKGROUND: Combined effect of both prenatal and early postnatal exposure to ambient air pollution on child cognition has rarely been investigated and periods of sensitivity are unknown. This study explores the temporal relationship between pre- and postnatal exposure to PM10, PM2.5, NO2 and child cognitive function. METHODS: Using validated spatiotemporally resolved exposure models, pre- and postnatal daily PM2.5, PM10 (satellite based, 1 km resolution) and NO2 (chemistry-transport model, 4 km resolution) concentrations at the mother's residence were estimated for 1271 mother-child pairs from the French EDEN and PELAGIE cohorts. Scores representative of children's General, Verbal and Non-Verbal abilities at 5-6 years were constructed based on subscale scores from the WPPSI-III, WISC-IV or NEPSY-II batteries, using confirmatory factor analysis (CFA). Associations of both prenatal (first 35 gestational weeks) and postnatal (60 months after birth) exposure to air pollutants with child cognition were explored using Distributed Lag Non-linear Models adjusted for confounders. RESULTS: Increased maternal exposure to PM10, PM2.5 and NO2, during sensitive windows comprised between the 15th and the 33rd gestational weeks, was associated with lower males' General and Non-verbal abilities. Higher postnatal exposure to PM2.5 between the 35th and 52nd month of life was associated with lower males' General, Verbal and Non-verbal abilities. Some protective associations were punctually observed for the very first gestational weeks or months of life for both males and females and the different pollutants and cognitive scores. DISCUSSION: These results suggest poorer cognitive function at 5-6 years among males following increased maternal exposure to PM10, PM2.5 and NO2 during mid-pregnancy and child exposure to PM2.5 around 3-4 years. Apparent protective associations observed are unlikely to be causal and might be due to live birth selection bias, chance finding or residual confounding.

Exposure of human fetal kidneys to mild analgesics interferes with early nephrogenesis.

Acetaminophen, aspirin, and ibuprofen are mild analgesics commonly used by pregnant women, the sole current recommendation being to avoid ibuprofen from the fifth month of gestation. The nephrotoxicity of these three analgesics is well documented in adults, as is their interference with prostaglandins biosynthesis. Here we investigated the effect of these analgesics on human first trimester kidneys ex vivo. We first evaluated prostaglandins biosynthesis functionality by performing a wide screening of prostaglandin expression patterns in first trimester human kidneys. We demonstrated that prostaglandins biosynthesis machinery is functional during early nephrogenesis. Human fetal kidney explants aged 7-12 developmental weeks were exposed ex vivo to ibuprofen, aspirin or acetaminophen for 7 days, and analyzed by histology, immunohistochemistry, and flow cytometry. This study has revealed that these analgesics induced a spectrum of abnormalities within early developing structures, ranging from cell death to a decline in differentiating glomeruli density. These results warrant caution for the use of these medicines during the first trimester of pregnancy.

Inverse probability weighting to handle attrition in cohort studies: some guidance and a call for caution.

BACKGROUND: Attrition in cohort studies challenges causal inference. Although inverse probability weighting (IPW) has been proposed to handle attrition in association analyses, its relevance has been little studied in this context. We aimed to investigate its ability to correct for selection bias in exposure-outcome estimation by addressing an important methodological issue: the specification of the response model. METHODS: A simulation study compared the IPW method with complete-case analysis (CCA) for nine response-mechanism scenarios (3 missing at random - MAR and 6 missing not at random - MNAR). Eighteen response models differing by the type of variables included were assessed. RESULTS: The IPW method was equivalent to CCA in terms of bias and consistently less efficient in all scenarios, regardless of the response model tested. The most effective response model included only the confounding factors of the association model. CONCLUSION: Our study questions the ability of the IPW method to correct for selection bias in situations of attrition leading to missing outcomes. If the method is to be used, we encourage including only the confounding variables of the association of interest in the response model.

Prenatal and childhood exposure to chlordecone and adiposity of seven-year-old children in the Timoun mother-child cohort study in Guadeloupe (French West Indies).

BACKGROUND: Exposure to persistent environmental organic pollutants may contribute to the development of obesity among children. Chlordecone is a persistent organochlorine insecticide with estrogenic properties that was used in the French West Indies (1973-1993) and is still present in the soil and the water and food consumed by the local population. We studied the association between prenatal and childhood exposure to chlordecone and the adiposity of prepubertal children. METHODS: Within the Timoun Mother-Child Cohort Study in Guadeloupe (French West Indies), 575 children had a medical examination at seven years of age, including adiposity measurements. A Structural Equation Modeling approach was used to create a global adiposity score from four adiposity indicators: the BMI z-score, percentage of fat mass, sum of the tricipital and subscapular skinfold thickness, and waist-to-height ratio. Chlordecone concentrations were measured in cord blood at birth and in the children's blood at seven years of age. Models were adjusted for prenatal and postnatal covariates. Sensitivity analyses accounted for co-exposure to PCB-153 and pp'-DDE. Mediation analyses, including intermediate birth outcomes, were conducted. RESULTS: Prenatal chlordecone exposure tended to be associated with increased adiposity at seven years of age, particularly in boys. However, statistical significance was only reached in the third quartile of exposure and neither linear nor non-linear trends could be formally identified. Consideration of preterm birth or birth weight in mediation analyses did not modify the results, as adjustment for PCB-153 and pp'-DDE co-exposures. CONCLUSION: Globally, we found little evidence of an association between chlordecone exposure during the critical in utero or childhood periods of development and altered body-weight homeostasis in childhood. Nevertheless, some associations we observed at seven years of age, although non-significant, were consistent with those observed at earlier ages and would be worth investing during further follow-ups of children of the Timoun Mother-Child Cohort Study when they reach puberty.

Key parameter optimization using multivariable linear model for the evaluation of the in vitro estrogenic activity assay in T47D cell lines (CXCL-test).

In comparison with analytical tools, bioassays provide higher sensitivity and more complex evaluation of environmental samples and are indispensable tools for monitoring increasing in anthropogenic pollution. Nevertheless, the disadvantage in cellular assays stems from the material variability used within the assays, and an interlaboratory adaptation does not usually lead to satisfactory test sensitivities. The aim of this study was to evaluate the influence of material variability on CXCL12 secretion by T47D cells, the outcome of the CXCL-test (estrogenic activity assay). For this purpose, the cell line sources, sera suppliers, experimental and seeding media, and the amount of cell/well were tested. The multivariable linear model (MLM), employed as an innovative approach in this field for parameter evaluation, identified that all the tested parameters had significant effects. Knowledge of the contributions of each parameter has permitted step-by-step optimization. The most beneficial approach was seeding 20,000 cells/well directly in treatment medium and using DMEM for the treatment. Great differences in both basal and maximal cytokine secretions among the three tested cell lines and different impacts of each serum were also observed. Altogether, both these biologically based and highly variable inputs were additionally assessed by MLM and a subsequent two-step evaluation, which revealed a lower variability and satisfactory reproducibility of the test. This analysis showed that not only parameter and procedure optimization but also the evaluation methodology must be considered from the perspective of interlaboratory method adaptation. This overall methodology could be applied to all bioanalytical methods for fast multiparameter and accurate analysis.

Prenatal exposure to pesticides and risk of preeclampsia among pregnant women: Results from the ELFE cohort.

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.

Changes in parental smoking during pregnancy and risks of adverse birth outcomes and childhood overweight in Europe and North America: An individual participant data meta-analysis of 229,000 singleton births.

BACKGROUND: Fetal smoke exposure is a common and key avoidable risk factor for birth complications and seems to influence later risk of overweight. It is unclear whether this increased risk is also present if mothers smoke during the first trimester only or reduce the number of cigarettes during pregnancy, or when only fathers smoke. We aimed to assess the associations of parental smoking during pregnancy, specifically of quitting or reducing smoking and maternal and paternal smoking combined, with preterm birth, small size for gestational age, and childhood overweight. METHODS AND FINDINGS: We performed an individual participant data meta-analysis among 229,158 families from 28 pregnancy/birth cohorts from Europe and North America. All 28 cohorts had information on maternal smoking, and 16 also had information on paternal smoking. In total, 22 cohorts were population-based, with birth years ranging from 1991 to 2015. The mothers' median age was 30.0 years, and most mothers were medium or highly educated. We used multilevel binary logistic regression models adjusted for maternal and paternal sociodemographic and lifestyle-related characteristics. Compared with nonsmoking mothers, maternal first trimester smoking only was not associated with adverse birth outcomes but was associated with a higher risk of childhood overweight (odds ratio [OR] 1.17 [95% CI 1.02-1.35], P value = 0.030). Children from mothers who continued smoking during pregnancy had higher risks of preterm birth (OR 1.08 [95% CI 1.02-1.15], P value = 0.012), small size for gestational age (OR 2.15 [95% CI 2.07-2.23], P value < 0.001), and childhood overweight (OR 1.42 [95% CI 1.35-1.48], P value < 0.001). Mothers who reduced the number of cigarettes between the first and third trimester, without quitting, still had a higher risk of small size for gestational age. However, the corresponding risk estimates were smaller than for women who continued the same amount of cigarettes throughout pregnancy (OR 1.89 [95% CI 1.52-2.34] instead of OR 2.20 [95% CI 2.02-2.42] when reducing from 5-9 to ≤4 cigarettes/day; OR 2.79 [95% CI 2.39-3.25] and OR 1.93 [95% CI 1.46-2.57] instead of OR 2.95 [95% CI 2.75-3.15] when reducing from ≥10 to 5-9 and ≤4 cigarettes/day, respectively [P values < 0.001]). Reducing the number of cigarettes during pregnancy did not affect the risks of preterm birth and childhood overweight. Among nonsmoking mothers, paternal smoking was associated with childhood overweight (OR 1.21 [95% CI 1.16-1.27], P value < 0.001) but not with adverse birth outcomes. Limitations of this study include the self-report of parental smoking information and the possibility of residual confounding. As this study only included participants from Europe and North America, results need to be carefully interpreted regarding other populations. CONCLUSIONS: We observed that as compared to nonsmoking during pregnancy, quitting smoking in the first trimester is associated with the same risk of preterm birth and small size for gestational age, but with a higher risk of childhood overweight. Reducing the number of cigarettes, without quitting, has limited beneficial effects. Paternal smoking seems to be associated, independently of maternal smoking, with the risk of childhood overweight. Population strategies should focus on parental smoking prevention before or at the start, rather than during, pregnancy.

Audiogenic seizure as a model of sudden death in epilepsy: A comparative study between four inbred mouse strains from early life to adulthood.

OBJECTIVE: Mouse models of sudden unexpected death in epileptic patients (SUDEP) using audiogenic seizures (AGS) are valuable because death can occur following a sound-induced seizure in the absence of any pharmacologic or electric component. However, only a few strains of mice are AGS prone, and the vast majority of studies involve DBA/2 or DBA/1 inbred strains. With the goal of characterizing the variation of AGS susceptibility with age, and of offering a larger panel of mice available for AGS studies, we performed a comparative study of the variability in AGS responses. METHODS: The variation of AGS with age was determined in two classically used inbred strains of mice, DBA/2 and DBA/1, and two additional strains, BALB/c and 129/SvTer. As AGS-stimulated tonic seizures can be lethal or nonlethal, even in the same inbred strain, in a second experiment, we addressed whether there is an innate capacity to reproduce the same response after a tonic AGS, referred to as "determinism," in the DBA/2J, DBA/1J, and 129/SvTer mouse strains. RESULTS: Results show that the 129/SvTer mouse is a more versatile model of SUDEP due to its wider age range of susceptibility compared to the DBA/2J and DBA/1J mouse strains. In addition, we show that determinism is not consistently evident in DBA/2J and 129/SvTer strains after AGS. Hence, one cannot be certain that a lethal AGS will always be lethal in successive testing after resuscitation and vice versa in these two mouse strains. SIGNIFICANCE: These studies highlight the phenotypic variability of AGS in different mouse strains, show the value of an additional mouse strain, 129/SvTer, for studies using AGS, and thus provide valuable information for future studies of AGS and SUDEP.

Maternal body mass index, gestational weight gain, and the risk of overweight and obesity across childhood: An individual participant data meta-analysis.

BACKGROUND: Maternal obesity and excessive gestational weight gain may have persistent effects on offspring fat development. However, it remains unclear whether these effects differ by severity of obesity, and whether these effects are restricted to the extremes of maternal body mass index (BMI) and gestational weight gain. We aimed to assess the separate and combined associations of maternal BMI and gestational weight gain with the risk of overweight/obesity throughout childhood, and their population impact. METHODS AND FINDINGS: We conducted an individual participant data meta-analysis of data from 162,129 mothers and their children from 37 pregnancy and birth cohort studies from Europe, North America, and Australia. We assessed the individual and combined associations of maternal pre-pregnancy BMI and gestational weight gain, both in clinical categories and across their full ranges, with the risks of overweight/obesity in early (2.0-5.0 years), mid (5.0-10.0 years) and late childhood (10.0-18.0 years), using multilevel binary logistic regression models with a random intercept at cohort level adjusted for maternal sociodemographic and lifestyle-related characteristics. We observed that higher maternal pre-pregnancy BMI and gestational weight gain both in clinical categories and across their full ranges were associated with higher risks of childhood overweight/obesity, with the strongest effects in late childhood (odds ratios [ORs] for overweight/obesity in early, mid, and late childhood, respectively: OR 1.66 [95% CI: 1.56, 1.78], OR 1.91 [95% CI: 1.85, 1.98], and OR 2.28 [95% CI: 2.08, 2.50] for maternal overweight; OR 2.43 [95% CI: 2.24, 2.64], OR 3.12 [95% CI: 2.98, 3.27], and OR 4.47 [95% CI: 3.99, 5.23] for maternal obesity; and OR 1.39 [95% CI: 1.30, 1.49], OR 1.55 [95% CI: 1.49, 1.60], and OR 1.72 [95% CI: 1.56, 1.91] for excessive gestational weight gain). The proportions of childhood overweight/obesity prevalence attributable to maternal overweight, maternal obesity, and excessive gestational weight gain ranged from 10.2% to 21.6%. Relative to the effect of maternal BMI, excessive gestational weight gain only slightly increased the risk of childhood overweight/obesity within each clinical BMI category (p-values for interactions of maternal BMI with gestational weight gain: p = 0.038, p < 0.001, and p = 0.637 in early, mid, and late childhood, respectively). Limitations of this study include the self-report of maternal BMI and gestational weight gain for some of the cohorts, and the potential of residual confounding. Also, as this study only included participants from Europe, North America, and Australia, results need to be interpreted with caution with respect to other populations. CONCLUSIONS: In this study, higher maternal pre-pregnancy BMI and gestational weight gain were associated with an increased risk of childhood overweight/obesity, with the strongest effects at later ages. The additional effect of gestational weight gain in women who are overweight or obese before pregnancy is small. Given the large population impact, future intervention trials aiming to reduce the prevalence of childhood overweight and obesity should focus on maternal weight status before pregnancy, in addition to weight gain during pregnancy.

Risk Factors for Shoulder Pain in a Cohort of French Workers: A Structural Equation Model.

Shoulder pain is common in the working population and causes loss of productivity, high economic costs, and long absences. Simultaneous evaluation of the complex relationships between work organization (e.g., work pace, application of quality standards), psychosocial and physical risk factors, stress, and shoulder pain is rare. The aim of this study was to explore the direct and indirect relationships between workplace risk factors, perceived stress, and occurrence of shoulder pain in workers of the Cohorte des Salariés Ligériens study. A total of 3,710 workers in a French region were randomly selected for inclusion between 2002 and 2005. They completed a self-administered questionnaire about musculoskeletal symptoms, individual factors, and exposure to work constraints. In 2007, they responded to a follow-up questionnaire. The study sample comprised 1,400 workers free of shoulder pain at baseline. Structural equation models were used. For both sexes, exposure to factors related to work organization had an effect on physical and psychosocial risk factors. Psychological demand was the only psychosocial constraint that increased perceived stress. Shoulder pain was influenced directly by physical risk factors for both sexes and by perceived stress for men. In view of their distal action, work organization is an important target for strategies to prevent shoulder pain in the working population.

Gestational weight gain charts for different body mass index groups for women in Europe, North America, and Oceania.

BACKGROUND: Gestational weight gain differs according to pre-pregnancy body mass index and is related to the risks of adverse maternal and child health outcomes. Gestational weight gain charts for women in different pre-pregnancy body mass index groups enable identification of women and offspring at risk for adverse health outcomes. We aimed to construct gestational weight gain reference charts for underweight, normal weight, overweight, and grades 1, 2 and 3 obese women and to compare these charts with those obtained in women with uncomplicated term pregnancies. METHODS: We used individual participant data from 218,216 pregnant women participating in 33 cohorts from Europe, North America, and Oceania. Of these women, 9065 (4.2%), 148,697 (68.1%), 42,678 (19.6%), 13,084 (6.0%), 3597 (1.6%), and 1095 (0.5%) were underweight, normal weight, overweight, and grades 1, 2, and 3 obese women, respectively. A total of 138, 517 women from 26 cohorts had pregnancies with no hypertensive or diabetic disorders and with term deliveries of appropriate for gestational age at birth infants. Gestational weight gain charts for underweight, normal weight, overweight, and grade 1, 2, and 3 obese women were derived by the Box-Cox t method using the generalized additive model for location, scale, and shape. RESULTS: We observed that gestational weight gain strongly differed per maternal pre-pregnancy body mass index group. The median (interquartile range) gestational weight gain at 40 weeks was 14.2 kg (11.4-17.4) for underweight women, 14.5 kg (11.5-17.7) for normal weight women, 13.9 kg (10.1-17.9) for overweight women, and 11.2 kg (7.0-15.7), 8.7 kg (4.3-13.4) and 6.3 kg (1.9-11.1) for grades 1, 2, and 3 obese women, respectively. The rate of weight gain was lower in the first half than in the second half of pregnancy. No differences in the patterns of weight gain were observed between cohorts or countries. Similar weight gain patterns were observed in mothers without pregnancy complications. CONCLUSIONS: Gestational weight gain patterns are strongly related to pre-pregnancy body mass index. The derived charts can be used to assess gestational weight gain in etiological research and as a monitoring tool for weight gain during pregnancy in clinical practice.

Long-term negative impact of an inappropriate first antiepileptic medication on the efficacy of a second antiepileptic medication in mice.

Childhood absence epilepsy (CAE) is one of the most frequent epilepsies in infancy. The first-line recommended therapy for CAE is based on the prescription of the narrow-spectrum ethosuximide and the broad-spectrum valproic acid, which have similar efficacy in the first 12 months. Nevertheless, some antiepileptic drugs (AEDs) may worsen seizure duration and type in this syndrome. In line with this, we have encountered a case of identical twins with CAE and early exposure to different antiseizure drugs leading to divergent outcomes. From this, we hypothesized that the first AED to treat CAE may determine the long-term prognosis, especially in the developing brain, and that some situations leading to drug resistance may be explained by use of an inappropriate first AED. Therefore, we investigated this hypothesis by using a genetic mouse model of absence epilepsy (BS/Orl). Mice received a first appropriate or inappropriate AED followed by the same appropriate AED. Our data demonstrate that an inappropriate first AED has a negative impact on the long-term efficacy of a second appropriate AED. This work supports the necessity to effectively diagnose epileptic syndromes prior to medication use, particularly in children, in order to prevent the deleterious effects of an inappropriate initial AED.

Factors determining the exposure of dairy farmers to thoracic organic dust.

Bronchial respiratory diseases are more common in dairy farmers than in the general population, perhaps because the repeated inhalation of organic dust contributes to the development of these disorders. However, the factors determining the exposure of farmers to particles that can enter the lower bronchial tract and interact with it, i.e. the thoracic fraction of the inhalable dust, remain to be identified. We therefore measured the exposure of dairy farmers to thoracic organic dust and identified the farm features and tasks that increased exposure. We measured thoracic particles (n = 110) and farm characteristics and occupational tasks in 29 Brittany dairy farms. The mean (GM) (geometric standard deviation, GSD) concentration of thoracic dust in air inhaled by farmers was 0.24 mg/m3 (2.8) and the concentrations of endotoxins, Gram-positive bacteria and fungi in the thoracic fraction were 128 EU/m3 (4.0), 960 CFU/m3 (6.3) and 690 CFU/m3 (5.4), respectively. Model-based estimates of the association between exposure, farm features and tasks indicated that manual grain and feed handling and mechanical bedding spreading significantly increased exposure to thoracic dust, endotoxins, bacteria and fungi. Exposure to bacteria and fungi was reduced by cowsheds divided into cubicles, whereas using automatic muck scrappers in alleyway and automatic milking tended to increase exposure to bacteria and endotoxins. Finally, exposure to endotoxin and fungi were reduced by warmer farm buildings and well-ventilated buildings having walls with large openings. In conclusions, major occupational tasks and specific farm features determine the exposure of Breton dairy farmers to thoracic organic dust.

Occupational exposure to organic solvents during pregnancy and childhood behavior: findings from the PELAGIE birth cohort (France, 2002-2013).

BACKGROUND: Numerous industries use organic solvents, and many workers from various occupational sectors are exposed to these known neurotoxicants, including pregnant women. Our objective is to explore whether occupational exposure of pregnant women to solvents may impair the neurodevelopment of their babies and consequently affect their behavior in childhood. METHODS: Within the French birth cohort PELAGIE, parents assessed their children's internalizing and externalizing behaviors using items from the Child Behavior Checklist and the Preschool Social Behavior Questionnaire at age 2, and the Strength and Difficulties Questionnaire at age 6. The occupational exposure to solvents of the pregnant women was self-reported prospectively at the beginning of their pregnancy (N = 715). We applied structural equation modeling to capture the longitudinal association of prenatal exposure to solvents with children's behavioral traits at 2 and 6 years. RESULTS: Increased externalizing behavior score at age 2 was associated with prenatal exposure to solvents (standardized score: 0.34 (95% CI = 0.11, 0.57) for occasional exposure and 0.26 (0.05, 0.48) for regular exposure). This association was attenuated at age 6 (0.22 (- 0.02, 0.47) for occasional exposure and 0.07 (- 0.14, 0.28) for regular exposure). No association was observed for internalizing behavior. CONCLUSIONS: Pregnant women's occupational exposure to solvents may affect their children's behavior in early childhood. This effect may be attenuated with aging or diluted by the effects of other postnatal predictors.

Correction to: Occupational exposure to organic solvents during pregnancy and childhood behavior: findings from the PELAGIE birth cohort (France, 2002-2013).

Following publication of the original article [1], the author asked to replace Table 2 with the correct version.

Estimating indoor galaxolide concentrations using predictive models based on objective assessments and data about dwelling characteristics.

BACKGROUND: Galaxolide (HHCB) is used for fragrance in many consumer products. The aim of the current study was to use objective assessments of HHCB to build a predictive model in order to estimate indoor-measured HHCB concentrations from questionnaire-based data on dwelling characteristics and occupants' habits and activities. METHODS: Environmental assessments of indoor HHCB, dwelling characteristics were carried out in 150 dwellings in Brittany (France). Among the various models that were tested, the best predictive model for the reduced set of characteristics was identified on the basis of the coefficient of determination (R2) criterion. RESULTS: Linear regression model showed among the best performances (R2 = 0.48), together with some more complex models. According to the estimated results, the main variables that significantly increased HHCB concentrations were: living in rural area, drying clothes inside dwellings, painted walls, chipboard furniture, double glazing, damaged floors and duration of bathroom door being kept open. Laminated floors and presence of indoor plants were found to significantly decrease HHCB concentrations. DISCUSSION: The linear model based on objective assessments and questionnaire-derived data about dwelling characteristics and occupants' activities constituted an easy method for predicting indoor air HHCB concentrations. For studies including a large number of dwellings, modeling of HHCB concentrations is cheaper than measuring it in every location. Our methodological procedure can be applied to other indoor air pollutants.

Drinking Water Disinfection By-products, Genetic Polymorphisms, and Birth Outcomes in a European Mother-Child Cohort Study.

BACKGROUND: We examined the association between exposure during pregnancy to trihalomethanes, the most common water disinfection by-products, and birth outcomes in a European cohort study (Health Impacts of Long-Term Exposure to Disinfection By-Products in Drinking Water). We took into account exposure through different water uses, measures of water toxicity, and genetic susceptibility. METHODS: We enrolled 14,005 mothers (2002-2010) and their children from France, Greece, Lithuania, Spain, and the UK. Information on lifestyle- and water-related activities was recorded. We ascertained residential concentrations of trihalomethanes through regulatory records and ad hoc sampling campaigns and estimated route-specific trihalomethane uptake by trimester and for whole pregnancy. We examined single nucleotide polymorphisms and copy number variants in disinfection by-product metabolizing genes in nested case-control studies. RESULTS: Average levels of trihalomethanes ranged from around 10 µg/L to above the regulatory limits in the EU of 100 µg/L between centers. There was no association between birth weight and total trihalomethane exposure during pregnancy (ß = 2.2 g in birth weight per 10 µg/L of trihalomethane, 95% confidence interval = 3.3, 7.6). Birth weight was not associated with exposure through different routes or with specific trihalomethane species. Exposure to trihalomethanes was not associated with low birth weight (odds ratio [OR] per 10 µg/L = 1.02, 95% confidence interval = 0.95, 1.10), small-for-gestational age (OR = 0.99, 0.94, 1.03) and preterm births (OR = 0.98, 0.9, 1.05). We found no gene-environment interactions for mother or child polymorphisms in relation to preterm birth or small-for-gestational age. CONCLUSIONS: In this large European study, we found no association between birth outcomes and trihalomethane exposures during pregnancy in the total population or in potentially genetically susceptible subgroups. (See video abstract at http://links.lww.com/EDE/B104.).