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1.  Home and Work Physical Activity Environments: Associations with Cardiorespiratory Fitness and Physical Activity Level in French Women 
The influence of the physical activity environment in the home and at work on cardiorespiratory fitness (CRF) and objectively-measured physical activity has not been extensively studied. We recruited 147 women with a (mean ± SD) age of 54 ± 7 years and without evidence of chronic disease. The physical activity environment was assessed by self-report (Assessing Levels of PHysical Activity or ALPHA questionnaire), CRF using a submaximal step test, usual physical activity using combined heart rate and accelerometry, as well as by a validated questionnaire (Recent Physical Activity Questionnaire). Summary scores of the home environment and the work environment derived from the ALPHA questionnaire were positively correlated with CRF after adjustment for age (r = 0.18, p = 0.03 and r = 0.28, p < 0.01, respectively). Women owning a bicycle or having a garden (which may prompt physical activity) had higher CRF; those with a bicycle at home also had a higher physical activity energy expenditure. Similarly, women who had access to fitness equipment at work had higher CRF. In conclusion, these results provide new insights into potential environmental influences on physical capacity and physical activity that could inform the design of physical activity promotion strategies.
doi:10.3390/ijerph13080824
PMCID: PMC4997510  PMID: 27537900
home environment; workplace environment; physical activity; physical fitness; aerobic capacity; accelerometer; heart rate; questionnaire
2.  Prenatal mercury contamination: relationship with maternal seafood consumption during pregnancy and fetal growth in the 'EDEN mother-child' cohort 
The British Journal of Nutrition  2010;104(8):1096-1100.
SUMMARY
Background
Maternal seafood intake is of great health interest since it constitutes an important source of n-3 fatty acids, but provides also an important pathway for fetal exposure to mercury (Hg).
Objectives
To determine associations between Hg contamination and both maternal seafood consumption and fetal growth in French pregnant women.
Design
Pregnant women included in the “EDEN mother-child” cohort study answered food frequency questionnaires on their usual diet in the year before and during the last three months of pregnancy, from which frequencies of seafood intake were evaluated. Total hair-Hg level was determined for the first 691 included women. Associations between Hg level, seafood intake and several neonatal measurements were studied using linear regressions adjusted for confounding variables.
Results
The median Hg level for mothers was 0.52 μg/g. Maternal seafood intake was associated with Hg level (r=0.33, p<0.0001). There was no association between Hg level and fetal growth in the whole sample of women, except for an early negative relation with biparietal diameter. A positive association was found between seafood intake and fetal growth in overweight women only which remained unchanged after adjustment for Hg level (birthweight: +101g for a difference of 1SD in seafood consumption, p=0.008).
Conclusions
Although seafood intake was associated with Hg contamination in French pregnant women, the contamination level was low. There was no consistent association between Hg level and fetal growth. Taking into account Hg level did not modify associations between seafood intake and fetal growth.
doi:10.1017/S0007114510001947
PMCID: PMC3095592  PMID: 20487582
Adult; Cohort Studies; Female; Fetal Growth Retardation; chemically induced; Food Contamination; Hair; chemistry; Humans; Infant, Newborn; Male; Mercury; analysis; toxicity; Pregnancy; Prenatal Exposure Delayed Effects; Seafood; Water Pollutants, Chemical; toxicity; Mercury; seafood consumption; prenatal exposure; fetal growth
3.  Monitoring the obesity epidemic in France: the Obepi surveys 1997-2006 
Obesity (Silver Spring, Md.)  2008;16(9):2182-2186.
The objective of the study is to describe the prevalences of obesity in French adults over a 9 year period. Mailed questionnaire surveys, in 1997, 2000, 2003 and 2006, sampled 20,000 representative French households by the method of quotas Weight, height and waist circumference were reported by all members of the selected households 18 years and older. Obesity was defined according to WHO criteria, BMI < 25 kg/m2.
The prevalence of adult obesity increased progressively from 8.6 % (95% confidence interval: 8.2–8.8) in 1997 to 13.1 % (12.7–13.5) in 2006. The increase affected all ages, socio economic strata and regions. While the prevalence of obesity increased in parallel in men and women from 1997 to 2003, the rate of increase was lower in men between 2003 and 2006.
These surveys showed a sharp increase in the prevalence of obesity in France in recent years contrasting with a stable prevalence in the 1980s. The results of the first Obepi surveys prompted the French government to implement a Nutrition and Health National Plan in 2001. Regular monitoring of obesity prevalence in France and neighboring countries is needed to compare future trends.
doi:10.1038/oby.2008.285
PMCID: PMC2665194  PMID: 18535547
Adolescent; Adult; Aged; Aged, 80 and over; Body Height; Body Mass Index; Body Weight; Disease Outbreaks; Female; France; epidemiology; Humans; Male; Middle Aged; Obesity; epidemiology; Overweight; epidemiology; Prevalence; Socioeconomic Factors; Waist Circumference; Young Adult; adults; epidemiology; prevalence; socioeconomics; obesity
4.  Epigenome-Wide Meta-Analysis of Methylation in Children Related to Prenatal NO2 Air Pollution Exposure 
Environmental Health Perspectives  2016;125(1):104-110.
Background:
Prenatal exposure to air pollution is considered to be associated with adverse effects on child health. This may partly be mediated by mechanisms related to DNA methylation.
Objectives:
We investigated associations between exposure to air pollution, using nitrogen dioxide (NO2) as marker, and epigenome-wide cord blood DNA methylation.
Methods:
We meta-analyzed the associations between NO2 exposure at residential addresses during pregnancy and cord blood DNA methylation (Illumina 450K) in four European and North American studies (n = 1,508) with subsequent look-up analyses in children ages 4 (n = 733) and 8 (n = 786) years. Additionally, we applied a literature-based candidate approach for antioxidant and anti-inflammatory genes. To assess influence of exposure at the transcriptomics level, we related mRNA expression in blood cells to NO2 exposure in 4- (n = 111) and 16-year-olds (n = 239).
Results:
We found epigenome-wide significant associations [false discovery rate (FDR) p < 0.05] between maternal NO2 exposure during pregnancy and DNA methylation in newborns for 3 CpG sites in mitochondria-related genes: cg12283362 (LONP1), cg24172570 (3.8 kbp upstream of HIBADH), and cg08973675 (SLC25A28). The associations with cg08973675 methylation were also significant in the older children. Further analysis of antioxidant and anti-inflammatory genes revealed differentially methylated CpGs in CAT and TPO in newborns (FDR p < 0.05). NO2 exposure at the time of biosampling in childhood had a significant impact on CAT and TPO expression.
Conclusions:
NO2 exposure during pregnancy was associated with differential offspring DNA methylation in mitochondria-related genes. Exposure to NO2 was also linked to differential methylation as well as expression of genes involved in antioxidant defense pathways.
Citation:
Gruzieva O, Xu CJ, Breton CV, Annesi-Maesano I, Antó JM, Auffray C, Ballereau S, Bellander T, Bousquet J, Bustamante M, Charles MA, de Kluizenaar Y, den Dekker HT, Duijts L, Felix JF, Gehring U, Guxens M, Jaddoe VV, Jankipersadsing SA, Merid SK, Kere J, Kumar A, Lemonnier N, Lepeule J, Nystad W, Page CM, Panasevich S, Postma D, Slama R, Sunyer J, Söderhäll C, Yao J, London SJ, Pershagen G, Koppelman GH, Melén E. 2017. Epigenome-wide meta-analysis of methylation in children related to prenatal NO2 air pollution exposure. Environ Health Perspect 125:104–110; http://dx.doi.org/10.1289/EHP36
doi:10.1289/EHP36
PMCID: PMC5226705  PMID: 27448387
5.  Correcting for the influence of sampling conditions on biomarkers of exposure to phenols and phthalates: a 2-step standardization method based on regression residuals 
Environmental Health  2012;11:29.
Background
Environmental epidemiology and biomonitoring studies typically rely on biological samples to assay the concentration of non-persistent exposure biomarkers. Between-participant variations in sampling conditions of these biological samples constitute a potential source of exposure misclassification. Few studies attempted to correct biomarker levels for this error. We aimed to assess the influence of sampling conditions on concentrations of urinary biomarkers of select phenols and phthalates, two widely-produced families of chemicals, and to standardize biomarker concentrations on sampling conditions.
Methods
Urine samples were collected between 2002 and 2006 among 287 pregnant women from Eden and Pélagie cohorts, from which phthalates and phenols metabolites levels were assayed. We applied a 2-step standardization method based on regression residuals. First, the influence of sampling conditions (including sampling hour, duration of storage before freezing) and of creatinine levels on biomarker concentrations were characterized using adjusted linear regression models. In the second step, the model estimates were used to remove the variability in biomarker concentrations due to sampling conditions and to standardize concentrations as if all samples had been collected under the same conditions (e.g., same hour of urine collection).
Results
Sampling hour was associated with concentrations of several exposure biomarkers. After standardization for sampling conditions, median concentrations differed by ‒ 38 % for 2,5-dichlorophenol to +80 % for a metabolite of diisodecyl phthalate. However, at the individual level, standardized biomarker levels were strongly correlated (correlation coefficients above 0.80) with unstandardized measures.
Conclusions
Sampling conditions, such as sampling hour, should be systematically collected in biomarker-based studies, in particular when the biomarker half-life is short. The 2-step standardization method based on regression residuals that we proposed in order to limit the impact of heterogeneity in sampling conditions could be further tested in studies describing levels of biomarkers or their influence on health.
doi:10.1186/1476-069X-11-29
PMCID: PMC3533777  PMID: 22537080
Biomarker; Endocrine Disruptor; Phenols; Phthalate esters; Pregnancy; Sampling conditions
6.  Maternal exposure to air pollution before and during pregnancy related to changes in newborn's cord blood lymphocyte subpopulations. The EDEN study cohort 
Background
Toxicants can cross the placenta and expose the developing fetus to chemical contamination leading to possible adverse health effects, by potentially inducing alterations in immune competence. Our aim was to investigate the impacts of maternal exposure to air pollution before and during pregnancy on newborn's immune system.
Methods
Exposure to background particulate matter less than 10 μm in diameter (PM10) and nitrogen dioxide (NO2) was assessed in 370 women three months before and during pregnancy using monitoring stations. Personal exposure to four volatile organic compounds (VOCs) was measured in a subsample of 56 non-smoking women with a diffusive air sampler during the second trimester of pregnancy. Cord blood was analyzed at birth by multi-parameter flow cytometry to determine lymphocyte subsets.
Results
Among other immunophenotypic changes in cord blood, decreases in the CD4+CD25+ T-cell percentage of 0.82% (p = 0.01), 0.71% (p = 0.04), 0.88% (p = 0.02), and 0.59% (p = 0.04) for a 10 μg/m3 increase in PM10 levels three months before and during the first, second and third trimester of pregnancy, respectively, were observed after adjusting for confounders. A similar decrease in CD4+CD25+ T-cell percentage was observed in association with personal exposure to benzene. A similar trend was observed between NO2 exposure and CD4+CD25+ T-cell percentage; however the association was stronger between NO2 exposure and an increased percentage of CD8+ T-cells.
Conclusions
These data suggest that maternal exposure to air pollution before and during pregnancy may alter the immune competence in offspring thus increasing the child's risk of developing health conditions later in life, including asthma and allergies.
doi:10.1186/1471-2393-11-87
PMCID: PMC3227583  PMID: 22047167
7.  Latent variables and structural equation models for longitudinal relationships: an illustration in nutritional epidemiology 
Background
The use of structural equation modeling and latent variables remains uncommon in epidemiology despite its potential usefulness. The latter was illustrated by studying cross-sectional and longitudinal relationships between eating behavior and adiposity, using four different indicators of fat mass.
Methods
Using data from a longitudinal community-based study, we fitted structural equation models including two latent variables (respectively baseline adiposity and adiposity change after 2 years of follow-up), each being defined, by the four following anthropometric measurement (respectively by their changes): body mass index, waist circumference, skinfold thickness and percent body fat. Latent adiposity variables were hypothesized to depend on a cognitive restraint score, calculated from answers to an eating-behavior questionnaire (TFEQ-18), either cross-sectionally or longitudinally.
Results
We found that high baseline adiposity was associated with a 2-year increase of the cognitive restraint score and no convincing relationship between baseline cognitive restraint and 2-year adiposity change could be established.
Conclusions
The latent variable modeling approach enabled presentation of synthetic results rather than separate regression models and detailed analysis of the causal effects of interest. In the general population, restrained eating appears to be an adaptive response of subjects prone to gaining weight more than as a risk factor for fat-mass increase.
doi:10.1186/1471-2288-10-37
PMCID: PMC2873513  PMID: 20433707
8.  High plasma leptin predicts an increase in subcutaneous adiposity in children and adults 
Objective
To investigate the hypothesis that plasma leptin may predict adiposity changes.
Design
A population-based cohort study.
Setting
Fleurbaix and Laventie, in the north of France.
Subjects
1175 subjects participated, of whom 946 completed measurements at baseline (1999) and follow-up (2001). After excluding 64 subjects obese at baseline, 882 subjects (478 adults, 404 children 8y and over) were included in the analysis.
Interventions
We measured plasma leptin concentrations at baseline and various adiposity parameters at baseline and follow-up. Partial correlation coefficients (rp) between baseline plasma leptin and each adiposity indicator at follow-up were calculated with adjustment for baseline age, pubertal stage, adiposity and familial correlations between siblings.
Results
Changes in body mass index and % body fat were not related to baseline plasma leptin. High baseline plasma leptin predicted an increase (rp (p value)) in the sum of the four skinfolds (0.18 (<0.0001)), the waist circumference (0.16 (0.0003)) and the waist-to-hip ratio (0.29 (<0.0001)) in adults only, and in the hip circumference in adults (0.20 (<0.0001)) and children (0.22 (<0.0001)). After adjustment for a set of 4 adiposity variables at baseline (% body fat, skinfolds, waist and hip circumferences), baseline plasma leptin predicted only changes in the sum of the four skinfolds in adults (0.15 (0.001)), with similar tendency although not significant in children (0.08 (0.13)).
Conclusions
A high leptin relative to baseline fat mass predicts fat mass gain over time, mainly in the subcutaneous location.
Sponsorship
Supported by Knoll, Centre d’Etudes et de Documentation du Sucre (CEDUS), Groupe Fournier, Lesieur, Nestlé France, Produits Roche, Le Centre d’Information Scientifique sur la Bière (CISB).
Descriptors
adipocytokins; insulin; adipose tissue; epidemiology
doi:10.1038/sj.ejcn.1602579
PMCID: PMC2093948  PMID: 17164827
Adult; Body Composition; Body Mass Index; Child; Cohort Studies; Female; Follow-Up Studies; France; Humans; Leptin; blood; Male; Obesity; blood; epidemiology; etiology; Predictive Value of Tests; Skinfold Thickness; Subcutaneous Fat; growth & development; metabolism; Waist-Hip Ratio; Weight Gain
9.  Changes in physical activity explain paradoxical relationship between baseline physical activity and adiposity changes in adolescent girls: the FLVS II study 
International Journal of Obesity  2005;29(6):586-593.
Objective
To investigate in adolescents, relationships between habitual physical activity (PA) and changes in several indicators of adiposity.
To investigate in adolescents from a population-based study, relationships between habitual physical activity (PA) and changes in several indicators of adiposity.
Design
Longitudinal population-based study. The Fleurbaix-Laventie Ville Santé II (FLVS II) study in northern France.
Subjects
A total of 222 boys and 214 girls aged 8–18 y, not obese at inclusion.
Measurements
PA (Modifiable Activity Questionnaire) and adiposity (BMI, % body fat by bio-impedance analysis, sum of 4 skinfolds, waist circumference) were assessed in 1999 and 2001. Adiposity indicators adjusted for age and pubertal stage were compared between groups of baseline PA and between groups of PA changes, separately by sex.
Results
At baseline, PA was not associated with adiposity indicators in both sexes. In girls only, being in the group with the highest age-relative level of moderate PA at baseline predicted the highest adiposity gain from baseline to follow-up, for all indicators. After adjustment for baseline values, all adiposity indicators were higher at follow-up in girls who had decreased their relative level of moderate PA during follow-up. In boys, changes in adiposity during follow-up were not significantly different across groups of PA changes. However, the sum of skinfolds at follow-up, adjusted for baseline value, tended to be higher in those who decreased their vigorous PA level and lower in those who increased it.
Conclusion
In adolescent girls, a decrease in PA rather than inactivity per se may result in increased adiposity over time.
doi:10.1038/sj.ijo.0802992
PMCID: PMC2043091  PMID: 15889117
Adipose Tissue; anatomy & histology; Adolescent; Age Factors; Body Composition; Body Mass Index; Chi-Square Distribution; Child; Exercise; Female; Humans; Longitudinal Studies; Male; Sex Factors; Skinfold Thickness
10.  Cardiovascular risk factor levels and their relationships with overweight and fat distribution in children: the Fleurbaix Laventie Ville Santé II study 
Metabolism  2007;56(5):614-622.
Objectives
To document for the first time in a general population of French children, the prevalence and levels of cardiovascular risk factors, and to assess, separately in boys and girls, whether these risk factors were associated with fat mass distribution independently of subcutaneous overall adiposity.
Subjects and design
A cross sectional analysis of baseline data from 452 children (235 boys and 217 girls) aged 8–17 years included in 1999 in a population-based epidemiologic study, the Fleurbaix Laventie Ville Santé II (FLVS II) study.
Methods
Overweight was defined according to the International Obesity Task Force (IOTF) references and to the 90th percentiles of the French BMI curves. The thresholds of parameters defining cardiovascular and metabolic risk were the 95th percentile of the Task Force Report on High Blood Pressure in Children and Adolescents for blood pressure, and those of the American Academy of Pediatrics for lipids. Anthropometric and biologic parameters were described by gender and according to overweight. Partial correlations between cardiovascular risk factors and anthropometric measures of adiposity (BMI, sum of four skinfold thicknesses, waist circumference, waist-to-height ratio) were calculated. In a second step, these correlations were additionally adjusted for the sum of four skinfold thicknesses.
Results
High plasma triglycerides, high insulin concentration and low plasma HDL cholesterol were associated with all measures of adiposity (|r|≥0.20; p<0.002). When obese children were excluded, overweight children already had high triglycerides and low HDL cholesterol levels respectively 2 and 20 times more frequently than normal weight children. Among overweight children, 7.7% had at least two risk factors among high blood pressure, high plasma triglycerides or glucose, and low HDL concentrations, versus 0.25% among normal weight children (p=0.002). After adjusting for the sum of skinfolds, an independent association between the risk factors and waist circumference was found in girls.
Conclusions
(a) Modest excess weight is associated with increased levels of cardiovascular risk factors. (b) In girls, abdominal fat distribution is associated with cardiovascular risk factors, independently of overall adiposity. (c) International definition of abdominal obesity in children is required to standardize studies and progress in the evaluation of childhood obesity and its consequences.
doi:10.1016/j.metabol.2006.12.006
PMCID: PMC1988890  PMID: 17445535
Abdominal Fat; Adolescent; Anthropometry; Blood Glucose; metabolism; Blood Pressure; physiology; Cardiovascular Diseases; blood; epidemiology; Child; Cholesterol; blood; Cross-Sectional Studies; Female; France; epidemiology; Humans; Insulin; blood; Male; Obesity; blood; epidemiology; Prevalence; Risk Factors; Triglycerides; blood
11.  Implication of the Pro12Ala polymorphism of the PPAR-gamma 2 gene in type 2 diabetes and obesity in the French population 
BMC Medical Genetics  2005;6:11.
Background
The Pro12Ala Single Nucleotide Polymorphism (SNP) of the Peroxisome Proliferator-Activated Receptor gamma 2 (PPAR-gamma 2) has been associated with insulin resistance and type 2 diabetes (T2D) and also inconsistently with obesity. The aim of this study was to evaluate the impact of this SNP with regards to T2D and childhood and adult obesity in the French Caucasian population.
Methods
We conducted three independent case/control studies encompassing 2126 cases and 1124 controls.
Results
We found a significant association between PPAR-gamma 2 Pro12Ala SNP and T2D (p = 0.04, OR = 1.37), which was stronger when the T2D cohort was stratified according to the obesity status (p = 0.03, OR = 1.81 in obese T2D subjects). In contrast, there was no association between the Pro12Ala SNP and childhood and adulthood obesity. In normal glucose tolerant obese adults (but not in lean subjects), the Pro12 allele was associated with a significant increase in fasting insulin levels (p = 0.01), and in insulin resistance estimated by the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) (p = 0.003), after adjustment for age, gender and BMI. We didn't detect evidence for an interaction effect between the Pro12Ala SNP and the obesity status with respect to the HOMA-IR index in normal glucose tolerant children, but we found a borderline interaction (p = 0.06) in normal glucose tolerant adults.
Conclusion
Our results showed that the Pro12Ala polymorphism is not associated with childhood or adult obesity in the French Caucasian population. In contrast, we confirm a contribution of the PPAR-gamma 2 Pro12 allele in the genetic risk forT2D, especially in obese subjects, where this allele worsens insulin resistanceand increases fasting insulin levels.
doi:10.1186/1471-2350-6-11
PMCID: PMC1084346  PMID: 15784141
12.  A Novel Method to Describe Early Offspring Body Mass Index (BMI) Trajectories and to Study Its Determinants 
PLoS ONE  2016;11(6):e0157766.
Background
Accurately characterizing children’s body mass index (BMI) trajectories and studying their determinants is a statistical challenge. There is a need to identify early public health measures for obesity prevention. We describe a method that allows studies of the determinants of height, weight and BMI growth up to five years of age. We illustrated this method using maternal smoking during pregnancy as one of the early-life factors that is potentially involved in prenatal programming of obesity.
Methods
Individual height and weight trajectories were fitted using the Jenss-Bayley model on 28,381 and 30,515 measurements, respectively, from 1,666 children to deduce BMI trajectories. We assessed global associations between smoking and growth trajectories and cross-sectional associations at specific ages.
Results
Children exposed in late pregnancy had a 0.24 kg/m2 (95% confidence interval: 0.07, 0.41) higher BMI at 5 years of age compared with non-exposed children. Although the BMIs of children exposed during late pregnancy became significantly higher compared with those of non-exposed children from 2 years onwards, the trajectories began to diverge during the first weeks of life.
Conclusion
Our method is relevant for studies on the relationships between individual-level exposures and the dynamics and shapes of BMI growth during childhood, including key features such as instantaneous growth velocities and the age or BMI value at the BMI infancy peak that benefit from the monotonic pattern of height and weight growth.
doi:10.1371/journal.pone.0157766
PMCID: PMC4915665  PMID: 27327164
13.  Early determinants of food liking among 5y-old children: a longitudinal study from the EDEN mother-child cohort 
Background
Identifying the determinants of child’s liking for different foods may help to prevent future choices of unhealthy food.
Objective
To study early-life food-related characteristics associated with child’s liking for different foods at 5y with a longitudinal study.
Design
1142 5y- old children completed a liking test for “fruit and vegetables”, “meat, fish and eggs”, desserts and cheese. Data related to maternal food intake before pregnancy, infant feeding during the first year of life, maternal feeding practices at 2y, child’s food intake at 3y, and child’s food neophobia from 1 to 4y were collected prospectively from the mother. The associations between these factors and child‘s liking for each category of foods were analyzed using structural equation modelling.
Results
High food neophobia at 4 y was related to lower child’s liking for all food groups. Maternal feeding practices at 2y were associated with liking for dessert: negatively for the practices allowing child to control his/her own food intake, positively for restriction of child’s food intake for weight reasons. Moreover, child’s food intake at 3y was positively associated with child’s liking for “fruit and vegetables” as well as for cheese. Finally, adherence to the infant feeding pattern “long breastfeeding, later introduction of main meal components and use of home-made products” was positively associated with child’s liking for meat/fish/eggs.
Conclusions
For all food groups, food neophobia was a common determinant of child’s liking for food at 5y, whereas other factors were associated with food liking for specific food groups.
Electronic supplementary material
The online version of this article (doi:10.1186/s12966-016-0342-5) contains supplementary material, which is available to authorized users.
doi:10.1186/s12966-016-0342-5
PMCID: PMC4753648  PMID: 26876058
Children; Food liking; Determinants; Food neophobia; Longitudinal
15.  Prenatal Exposure to Phenols and Growth in Boys 
Epidemiology (Cambridge, Mass.)  2014;25(5):625-635.
Background
Phenols interact with nuclear receptors implicated in growth and adipogenesis regulation. Only a few studies have explored their effects on growth in humans.
Objectives
We studied the associations of maternal exposure to phenols during pregnancy with prenatal and postnatal growth of male newborns.
Methods
Within a cohort of women recruited during pregnancy, we selected 520 mother–son pairs and quantified 9 phenols in spot urine samples collected during pregnancy. We used ultrasonography during pregnancy, together with birth measurements, to assess fetal growth. We modeled individual postnatal growth trajectories from repeated measures of weight and height in the first 3 years of life.
Results
Triclosan concentration was negatively associated with growth parameters measured at the third ultrasound examination but not earlier in pregnancy. At birth, this phenol tended to be negatively associated with head circumference (−1.2 mm for an interquartile range [IQR] increase in ln-transformed triclosan concentration [95% confidence interval = −2.6 to 0.3]) but not with weight or height. Parabens were positively associated with weight at birth. This positive association remained for 3 years for methylparaben (β = 193 g [−4 to 389]) for an IQR increase in ln-transformed concentrations.
Conclusion
We relied on only 1 spot urine sample to assess exposure; because of the high variability in phenol urinary concentrations reported during pregnancy, using only 1 sample may result in exposure misclassification, in particular for bisphenol A. Our study suggested associations between prenatal exposure to parabens and triclosan and prenatal or early postnatal growth.
doi:10.1097/EDE.0000000000000132
PMCID: PMC4724208  PMID: 25061923
16.  Multidimensionality of the relationship between social status and dietary patterns in early childhood: longitudinal results from the French EDEN mother-child cohort 
Background
The association between socioeconomic position and diet in early childhood has mainly been addressed based on maternal education and household income. We aimed to assess the influence of a variety of social factors from different socio-ecological levels (parents, household and child-care) on multi-time point dietary patterns identified from 2 to 5 y.
Method
This study included 974 children from the French EDEN mother-child cohort. Two multi-time point dietary patterns were derived in a previous study: they correspond to consistent exposures to either core- or non-core foods across 2, 3 and 5 y and were labelled “Guidelines” and “Processed, fast-foods”. The associations of various social factors collected during pregnancy (age, education level) or at 2-y follow-up (mother’s single status, occupation, work commitments, household financial disadvantage, presence of older siblings and child-care arrangements) with each of the two dietary patterns, were assessed by multivariable linear regression analysis.
Results
The adherence to a diet close to “Guidelines” was positively and independently associated with both maternal and paternal education levels. The adherence to a diet consistently composed of processed and fast-foods was essentially linked with maternal variables (younger age and lower education level), household financial disadvantage, the presence of older sibling (s) and being cared for at home by someone other than the mother.
Conclusions
Multiple social factors operating at different levels (parents, household, and child-care) were found to be associated with the diet of young children. Different independent predictors were found for each of the two longitudinal dietary patterns, suggesting distinct pathways of influence. Our findings further suggest that interventions promoting healthier dietary choices for young children should involve both parents and take into account not only household financial disadvantage but also maternal age, family size and options for child-care.
doi:10.1186/s12966-015-0285-2
PMCID: PMC4581045  PMID: 26399708
Dietary patterns; Toddlers; Preschool children; Socio-economic position; Social inequalities
17.  Effectiveness of two year balance training programme on prevention of fall induced injuries in at risk women aged 75-85 living in community: Ossébo randomised controlled trial 
Objective To assess the effectiveness of a two year exercise programme of progressive balance retraining in reducing injurious falls among women aged 75-85 at increased risk of falls and injuries and living in the community.
Design Pragmatic multicentre, two arm, parallel group, randomised controlled trial.
Setting 20 study sites in 16 medium to large cities throughout France.
Participants 706 women aged 75-85, living in their own home, and with diminished balance and gait capacities, randomly allocated to the experimental intervention group (exercise programme, n=352) or the control group (no intervention, n=354).
Intervention Weekly supervised group sessions of progressive balance training offered in community based premises for two years, supplemented by individually prescribed home exercises.
Outcome measures A geriatrician blinded to group assignment classified falls into one of three categories (no consequence, moderate, severe) based on physical damage and medical care. The primary outcome was the rate of injurious falls (moderate and severe). The two groups were compared for rates of injurious falls with a “shared frailty” model. Other outcomes included the rates of all falls, physical functional capacities (balance and motor function test results), fear of falling (FES-I), physical activity level, and perceived health related quality of life (SF-36). Analysis was by intention to treat.
Results There were 305 injurious falls in the intervention group and 397 in the control group (hazard ratio 0.81, 95% confidence interval 0.67 to 0.99). The difference in severe injuries (68 in intervention group v 87 in control group) was of the same order of magnitude (0.83, 0.60 to 1.16). At two years, women in the intervention group performed significantly better on all physical tests and had significantly better perception of their overall physical function than women in the control group. Among women who started the intervention (n=294), the median number of group sessions attended was 53 (interquartile range 16-71). Five injurious falls related to the intervention were recorded.
Conclusion A two year progressive balance retraining programme combining weekly group and individual sessions was effective in reducing injurious falls and in improving measured and perceived physical function in women aged 75-85 at risk of falling.
Trial registration ClinicalTrials.gov (NCT00545350).
doi:10.1136/bmj.h3830
PMCID: PMC4511529  PMID: 26201510
18.  Effectiveness of two year balance training programme on prevention of fall induced injuries in at risk women aged 75-85 living in community: Ossébo randomised controlled trial 
The BMJ  2015;351:h3830.
Objective To assess the effectiveness of a two year exercise programme of progressive balance retraining in reducing injurious falls among women aged 75-85 at increased risk of falls and injuries and living in the community.
Design Pragmatic multicentre, two arm, parallel group, randomised controlled trial.
Setting 20 study sites in 16 medium to large cities throughout France.
Participants 706 women aged 75-85, living in their own home, and with diminished balance and gait capacities, randomly allocated to the experimental intervention group (exercise programme, n=352) or the control group (no intervention, n=354).
Intervention Weekly supervised group sessions of progressive balance training offered in community based premises for two years, supplemented by individually prescribed home exercises.
Outcome measures A geriatrician blinded to group assignment classified falls into one of three categories (no consequence, moderate, severe) based on physical damage and medical care. The primary outcome was the rate of injurious falls (moderate and severe). The two groups were compared for rates of injurious falls with a “shared frailty” model. Other outcomes included the rates of all falls, physical functional capacities (balance and motor function test results), fear of falling (FES-I), physical activity level, and perceived health related quality of life (SF-36). Analysis was by intention to treat.
Results There were 305 injurious falls in the intervention group and 397 in the control group (hazard ratio 0.81, 95% confidence interval 0.67 to 0.99). The difference in severe injuries (68 in intervention group v 87 in control group) was of the same order of magnitude (0.83, 0.60 to 1.16). At two years, women in the intervention group performed significantly better on all physical tests and had significantly better perception of their overall physical function than women in the control group. Among women who started the intervention (n=294), the median number of group sessions attended was 53 (interquartile range 16-71). Five injurious falls related to the intervention were recorded.
Conclusion A two year progressive balance retraining programme combining weekly group and individual sessions was effective in reducing injurious falls and in improving measured and perceived physical function in women aged 75-85 at risk of falling.
Trial registration ClinicalTrials.gov (NCT00545350).
doi:10.1136/bmj.h3830
PMCID: PMC4511529  PMID: 26201510
19.  Should the WHO Growth Charts Be Used in France? 
PLoS ONE  2015;10(3):e0120806.
Background
Growth charts are an essential clinical tool for evaluating a child's health and development. The current French reference curves, published in 1979, have recently been challenged by the 2006 World Health Organization (WHO) growth charts.
Objective
To evaluate and compare the growth of French children who were born between 1981 and 2007, with the WHO growth charts and the French reference curves currently used.
Design
Anthropometric measurements from French children, who participated in 12 studies, were analyzed: 82,151 measurements were available for 27,257 children in different age groups, from birth to 18 years. We calculated and graphically compared mean z-scores based on the WHO and French curves, for height, weight and Body Mass Index (BMI) according to age and sex. The prevalence of overweight using the WHO, the French and International Obesity Task Force definitions were compared.
Results
Our population of children was on average 0.5 standard deviations taller than the French reference population, from the first month of life until puberty age. Mean z-scores for height, weight and BMI were closer to zero based on the WHO growth charts than on the French references from infancy until late adolescence, except during the first six months. These differences not related to breastfeeding rates. As expected, the prevalence of overweight depended on the reference used, and differences varied according to age.
Conclusion
The WHO growth charts may be appropriate for monitoring growth of French children, as the growth patterns in our large population of French children were closer to the WHO growth charts than to the French reference curves, from 6 months onwards. However, there were some limitations in the use of these WHO growth charts, and further investigation is needed.
doi:10.1371/journal.pone.0120806
PMCID: PMC4356547  PMID: 25761138
20.  Degree of methylation of ZAC1 (PLAGL1) is associated with prenatal and post-natal growth in healthy infants of the EDEN mother child cohort 
Epigenetics  2013;9(3):338-345.
The ZAC1 gene, mapped to the 6q24 region, is part of a network of co-regulated imprinted genes involved in the control of embryonic growth. Loss of methylation at the ZAC1 differentially methylated region (DMR) is associated with transient neonatal diabetes mellitus, a developmental disorder involving growth retardation and diabetes in the first weeks of post-natal life. We assessed whether the degree of methylation of the ZAC1 DMR in leukocytes DNA extracted from cord blood is associated with fetal, birth and post-natal anthropometric measures or with C-peptide concentrations in cord serum. We also searched for an influence of dietary intake and maternal parameters on ZAC1 DMR methylation. We found positive correlations between the ZAC1 DMR methylation index (MI) and estimated fetal weight (EFW) at 32 weeks of gestation, weight at birth and weight at one year of age (respectively, r = 0.15, 0.09, 0.14; P values = 0.01, 0.15, 0.03). However, there were no significant correlations between the ZAC1 DMR MI and cord blood C-peptide levels. Maternal intakes of alcohol and of vitamins B2 were positively correlated with ZAC1 DMR methylation (respectively, r = 0.2 and 0.14; P = 0.004 and 0.04). The influence of ZAC1 seems to start in the second half of pregnancy and continue at least until the first year of life. The maternal environment also appears to contribute to the regulation of DNA methylation.
doi:10.4161/epi.27387
PMCID: PMC4053452  PMID: 24316753
ZAC1/HYMAI imprinted locus; imprinting disorders; transient neonatal diabetes mellitus; C-peptide; metabolism disorders; insulin secretion in vivo; nutrition and epigenetic regulation; pathophysiology and metabolism; fetal development
21.  Predicting changes in language skills between 2 and 3 years in the EDEN mother–child cohort 
PeerJ  2014;2:e335.
Objective. To examine the factors predicting changes in language skills between 2 and 3 years.
Methods. By using longitudinal data concerning 1002 children from the EDEN study, linear regression was used to predict 3-year language performance from 2-year language performance and the risk factors associated with language delays. Logistic regressions were performed to examine two change trajectories: children who fall below the 10th percentile of language skills between 2 and 3 years (declining trajectory), and those who rose above the 10th percentile (resilient trajectory).
Results. The final linear model accounted for 43% of the variance in 3-year language scores, with 2-year language scores accounting for 22%. Exposure to alcohol during pregnancy, earlier birth term, lower level of parental education and lower frequency of maternal stimulation were associated with the declining trajectory. Breastfeeding was associated with the resilient trajectory.
Conclusions. This study provides a better understanding of the natural history of early language delays by identifying biological and social factors that predict changes in language skills between the ages of 2 and 3 years.
doi:10.7717/peerj.335
PMCID: PMC3976115  PMID: 24749012
Language delays; Longitudinal study; Child; Preschool; Trajectory
22.  Validity of Electronically Administered Recent Physical Activity Questionnaire (RPAQ) in Ten European Countries 
PLoS ONE  2014;9(3):e92829.
Objective
To examine the validity of the Recent Physical Activity Questionnaire (RPAQ) which assesses physical activity (PA) in 4 domains (leisure, work, commuting, home) during past month.
Methods
580 men and 1343 women from 10 European countries attended 2 visits at which PA energy expenditure (PAEE), time at moderate-to-vigorous PA (MVPA) and sedentary time were measured using individually-calibrated combined heart-rate and movement sensing. At the second visit, RPAQ was administered electronically. Validity was assessed using agreement analysis.
Results
RPAQ significantly underestimated PAEE in women [median(IQR) 34.1 (22.1, 52.2) vs. 40.6 (32.4, 50.9) kJ/kg/day, 95%LoA: −44.4, 63.4 kJ/kg/day) and in men (43.7 (29.0, 69.0) vs. 45.5 (34.1, 57.6) kJ/kg/day, 95%LoA: −47.2, 101.3 kJ/kg/day]. Using individualised definition of 1MET, RPAQ significantly underestimated MVPA in women [median(IQR): 62.1 (29.4, 124.3) vs. 73.6 (47.8, 107.2) min/day, 95%LoA: −130.5, 305.3 min/day] and men [82.7 (38.8, 185.6) vs. 83.3 (55.1, 125.0) min/day, 95%LoA: −136.4, 400.1 min/day]. Correlations (95%CI) between subjective and objective estimates were statistically significant [PAEE: women, rho = 0.20 (0.15–0.26); men, rho = 0.37 (0.30–0.44); MVPA: women, rho = 0.18 (0.13–0.23); men, rho = 0.31 (0.24–0.39)]. When using non-individualised definition of 1MET (3.5 mlO2/kg/min), MVPA was substantially overestimated (∼30 min/day). Revisiting occupational intensity assumptions in questionnaire estimation algorithms with occupational group-level empirical distributions reduced median PAEE-bias in manual (25.1 kJ/kg/day vs. −9.0 kJ/kg/day, p<0.001) and heavy manual workers (64.1 vs. −4.6 kJ/kg/day, p<0.001) in an independent hold-out sample.
Conclusion
Relative validity of RPAQ-derived PAEE and MVPA is comparable to previous studies but underestimation of PAEE is smaller. Electronic RPAQ may be used in large-scale epidemiological studies including surveys, providing information on all domains of PA.
doi:10.1371/journal.pone.0092829
PMCID: PMC3965465  PMID: 24667343
23.  Maternal weight change before pregnancy in relation to birthweight and risks of adverse pregnancy outcomes 
European Journal of Epidemiology  2011;26(10):789-796.
Maternal weight change before pregnancy can be considered an indicator of maternal energy balance and nutritional status before conception, and may be involved in early life programming. We aimed to investigate the association of maternal Weight Change Before Pregnancy (WCBP) with fetal growth and adverse pregnancy outcomes. Data are from the French EDEN mother-child cohort of 1756 mother-child pairs; information on mother’s weight at 20 years, weight just before pregnancy, fetal anthropometry at second and third trimesters, infant’s birthweight and pregnancy complications were recorded. The average annual WCBP between 20 years and start of pregnancy (in kg/year) was categorized as: “Weight Loss” (n=320), “Moderate weight gain” (n=721) and “High weight gain” (n=715). The associations of WCBP with fetal and newborn characteristics and with adverse pregnancy outcomes were analyzed, adjusting for maternal and pregnancy characteristics, including the mother’s prepregnancy BMI. Interactions between WCBP and prepregnancy BMI were tested. Birthweight and estimated fetal weight in the third trimester increased significantly with increasing WCBP in mothers with BMI <25kg/m2. In these mothers, weight loss before pregnancy was associated with a higher risk of newborns small for gestational age (SGA). Whatever the prepregnancy BMI, WCBP was positively associated with a maternal risk of gestational diabetes and hypertension. The ponderal history of mothers before pregnancy can impact on fetal growth and on pregnancy outcomes such as gestational diabetes or hypertension. Our analysis is the first to report that in non-overweight women, those who lost weight before pregnancy are at higher risk of having SGA newborns.
doi:10.1007/s10654-011-9599-9
PMCID: PMC3925097  PMID: 21710259
Adult; Birth Weight; Body Mass Index; Cohort Studies; Female; Fetal Development; France; Gestational Age; Hospitals, Teaching; Humans; Mothers; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Pregnancy Trimester, Second; Pregnancy Trimester, Third; Questionnaires; Socioeconomic Factors; Weight Gain; physiology; Weight change; birthweight; adverse pregnancy outcomes
24.  The effect of fall prevention exercise programmes on fall induced injuries in community dwelling older adults: systematic review and meta-analysis of randomised controlled trials 
The BMJ  2013;347:f6234.
Objective To determine whether, and to what extent, fall prevention exercise interventions for older community dwelling people are effective in preventing different types of fall related injuries.
Data sources Electronic databases (PubMed, the Cochrane Library, Embase, and CINAHL) and reference lists of included studies and relevant reviews from inception to July 2013.
Study selection Randomised controlled trials of fall prevention exercise interventions, targeting older (>60 years) community dwelling people and providing quantitative data on injurious falls, serious falls, or fall related fractures.
Data synthesis Based on a systematic review of the case definitions used in the selected studies, we grouped the definitions of injurious falls into more homogeneous categories to allow comparisons of results across studies and the pooling of data. For each study we extracted or calculated the rate ratio of injurious falls. Depending on the available data, a given study could contribute data relevant to one or more categories of injurious falls. A pooled rate ratio was estimated for each category of injurious falls based on random effects models.
Results 17 trials involving 4305 participants were eligible for meta-analysis. Four categories of falls were identified: all injurious falls, falls resulting in medical care, severe injurious falls, and falls resulting in fractures. Exercise had a significant effect in all categories, with pooled estimates of the rate ratios of 0.63 (95% confidence interval 0.51 to 0.77, 10 trials) for all injurious falls, 0.70 (0.54 to 0.92, 8 trials) for falls resulting in medical care, 0.57 (0.36 to 0.90, 7 trials) for severe injurious falls, and 0.39 (0.22 to 0.66, 6 trials) for falls resulting in fractures, but significant heterogeneity was observed between studies of all injurious falls (I2=50%, P=0.04).
Conclusions Exercise programmes designed to prevent falls in older adults also seem to prevent injuries caused by falls, including the most severe ones. Such programmes also reduce the rate of falls leading to medical care.
doi:10.1136/bmj.f6234
PMCID: PMC3812467  PMID: 24169944
25.  Child and parent characteristics related to parental feeding practices. A cross-cultural examination in the US and France 
Appetite  2008;52(1):10.1016/j.appet.2008.08.007.
Although cross-cultural research between France and the United States has contributed to our understanding of adult eating habits, no research to date has considered differences in the way that French and American parents feed their children. American mothers (n = 59) and fathers (n = 38) and French mothers (n = 72) and fathers (n = 50) provided information about the feeding practices that they use with their children. U.S. parents reported higher levels of non-nutritive feeding practices and child control over feeding, whereas French parents reported greater monitoring and restriction of their child's food intake for weight reasons. Feeding practices were linked to child Body Mass Index (BMI) in both socio-cultural contexts.
doi:10.1016/j.appet.2008.08.007
PMCID: PMC3808174  PMID: 18789986
Feeding practices; Preschool children; Socio-cultural factors; Parenting

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