Meconium Concentrations of Pesticides and Risk of Hypospadias: A Case-Control Study in Brittany, France.

BACKGROUND: Hypospadias is a male genital tract defect for which an increase in prevalence has been documented over the last few decades. A role for environmental risk factors is suspected, including prenatal exposure to pesticides. OBJECTIVES: To study the risk of hypospadias in association with multiple pesticide measurements in meconium samples. METHODS: The Brittany Registry of Congenital Anomalies (France) conducted a case-control study between 2012 and 2018. Cases were hypospadias, ascertained by a pediatrician and a pediatric surgeon, excluding genetic conditions, following European Surveillance of Congenital Anomalies guidelines (N = 69). Controls (N = 135) were two male infants without congenital anomaly born after each case in the same maternity unit. Mothers in the maternity units completed a self-administered questionnaire, we collected medical data from hospital records, and medical staff collected meconium samples. We performed chemical analysis of 38 pesticides (parent compound and/or metabolite) by UHPLC/MS/MS following strict quality assurance/quality control criteria and blind to case-control status. We carried out logistic regression accounting for frequency-matching variables and major risk factors. RESULTS: Among the 38 pesticides measured, 16 (42%) were never detected in the meconium samples, 18 (47%) were in <5% of samples, and 4 (11%) in ≥5% of the samples. We observed an association between the detection of fenitrothion in meconium and the risk of hypospadias (OR = 2.6 [1.0-6.3] with n cases = 13, n controls = 21), but not the other pesticides. CONCLUSIONS: Our small study provides a robust assessment of fetal exposure. Fenitrothion's established antiandrogenic activities provide biologic plausibility for our observations. Further studies are needed to confirm this hypothesis.

Epidemiology of aplasia cutis congenita: A population-based study in Europe.

BACKGROUND: Aplasia cutis congenita (ACC) is a rare congenital anomaly characterized by localized or widespread absence of skin at birth, mainly affecting the scalp. Most information about ACC exists as individual case reports and medium-sized studies. OBJECTIVES: This study aimed to investigate the epidemiology of ACC, using data from a large European network of population-based registries for congenital anomalies (EUROCAT). METHODS: Twenty-eight EUROCAT population-based registries in 16 European countries were involved. Poisson regression models were exploited to estimate the overall and live birth prevalence, to test time trends in prevalence between four 5-year periods and to evaluate the impact of the change of coding for ACC from the unspecific ICD9-BPA code to the specific ICD10 code. Proportions of ACC cases associated with other anomalies were reported. RESULTS: Five hundred cases were identified in the period 1998-2017 (prevalence: 5.10 per 100,000 births). Prevalence across 5-year periods did not differ significantly and no significant differences were evident due to the change from ICD9 to ICD10 in ACC coding. Heterogeneity in prevalence was observed across registries. The scalp was the most common site for ACC (96.4%) and associated congenital anomalies were present in 33.8% of cases. Patau and Adams-Oliver syndromes were the most frequent among the associated chromosomal anomalies (88.3%) and the associated genetic syndromes (57.7%), respectively. 16% of cases were associated with limb anomalies and 15.4% with congenital heart defects. A family history of ACC was found in 2% of cases. CONCLUSION: To our knowledge, this is the only population-based study on ACC. The EUROCAT methodologies provide reliable prevalence estimates and proportions of associated anomalies.

Prenatal exposure to organophosphate pesticides and autism spectrum disorders in 11-year-old children in the French PELAGIE cohort.

BACKGROUND: Organophosphate (OP) pesticides act by inhibiting acetylcholinesterase activity at synaptic junctions and have already been linked with deleterious effects on neurodevelopment, including autism spectrum disorders (ASD). OBJECTIVES: To investigate the association of prenatal exposure to OP pesticides with traits related to ASD in 11-year-old children. METHODS: The "Childhood Autism Spectrum Test" (CAST) parent questionnaire was used to screen for autistic traits in 792 children from the French PELAGIE cohort. Prenatal maternal urine samples were collected <19 weeks of gestation in which metabolites of organophosphate insecticides were assessed for 185 of them. Negative binomial regression models were performed to explore the association between the CAST score and 8 groups of urine components, adjusted for potential ASD risk factors. RESULTS: In these urine samples, dialkylphosphates (DAP) were detected most often (>80%), terbufos and its metabolites least often (<10%). No association with ASD was found for DAP, terbufos or its metabolites. Incidence rate ratios (IRRs) increased with maternal urinary diazinon concentrations, from 1.11 (95% CI: 0.87-1.42) to 1.17 (95% CI: 0.94-1.46). Higher CAST scores were statistically significantly associated with the maternal urine samples in which chlorpyrifos or two of its metabolites (chlorpyrifos-oxon and 3,5,6-trichloro-2-pyridinol) were detected. The IRR for exposure to chlorpyrifos or chlorpyrifos-oxon was 1.27 (95%CI: 1.05-1.52) among all children, and 1.39 (95%CI: 1.07-1.82) among boys. CONCLUSION: These findings suggest an increase in autistic traits among 11-year-old children in association with prenatal maternal exposure to chlorpyrifos and possibly diazinon. These associations were previously suspected in the literature, in particular for chlorpyrifos. Further work establishing the causal mechanisms behind these risk association is needed.

In Utero Chlordecone Exposure and Thyroid, Metabolic, and Sex-Steroid Hormones at the Age of Seven Years: A Study From the TIMOUN Mother-Child Cohort in Guadeloupe.

Background: Chlordecone is an endocrine-disrupting chemical with well recognized estrogenic and progestagenic properties. This organochlorine insecticide was extensively used in the French West Indies from 1973 to 1993 to control the banana root borer. Due to its poor degradation in the environment, permanently polluted soil is responsible for the current contamination of the food chain and human beings. We aimed to examine the relationship of in utero exposure to chlordecone and thyroid (thyroid stimulating hormone [TSH], free tri-iodothyronine [FT3], free thyroxine [FT4]), metabolic (insulin growth-factor 1, leptin, adiponectin), and sex-steroid (dehydroepiandrosterone [DHEA], total testosterone [TT], dihydrotestosterone [DHT], estradiol [E2]) hormone levels in children at the age of seven years who participated in TIMOUN, an ongoing birth cohort in Guadeloupe. Methods: Chlordecone concentrations were measured in cord-blood at delivery. Thyroid, metabolic, and sex-steroid hormone levels were determined in the blood of children at seven years of age. Associations between in utero chlordecone exposure and hormone levels at seven years of age were assessed by multiple linear or logistic regression, controlling for confounding factors. Results: Among the study population (210 boys and 228 girls), chlordecone and hormone measurements were available for 124 boys and 161 girls. We found the third quartile of in utero chlordecone exposure relative to the lowest quartile to be associated with elevated TSH levels in girls and elevated DHEA, TT, and DHT levels in both sexes. Complementary non-linear analysis (spline regression) confirmed a significant non-linear trend for TSH in girls and DHEA and DHT in boys. Conclusion: In utero chlordecone exposure was associated with elevated levels of selected thyroid (TSH) and sex-steroid (DHEA, TT, and DHT) hormones at seven years in a non-monotonic dose response (inverted U) relationship. The implications for future health and reproductive function in puberty and adulthood should be determined.

Petroleum and Chlorinated Solvents in Meconium and the Risk of Hypospadias: A Pilot Study.

Background: Hypospadias is a male congenital malformation that occurs in ~2 of 1,000 births. The association between hypospadias and fetal exposure to environmental chemicals has been studied, but the results are inconsistent. Although several petroleum and chlorinated solvents are suspected to have teratogenic effects, their role in the occurrence of hypospadias has been little studied and never using biomarkers of exposure. We aimed to evaluate the association between fetal exposure to petroleum and chlorinated solvents measured in meconium and the occurrence of hypospadias. Methods: We conducted a pilot case-control study in the maternity of the University Hospital of Rennes (France). Eleven cases of hypospadias and 46 controls were recruited between October 2012 and January 2014. Data from hospital records and maternal self-reported questionnaires, including socio-demographic characteristics and occupational and non-occupational exposure to chemicals, were collected. Meconium samples were collected using a standardized protocol. Levels of petroleum solvents (toluene, benzene, ethylbenzene, and p, m, and o xylene), certain metabolites (mandelic acid, hippuric acid, methylhippuric acid, S-phenylmercapturic acid, S-benzylmercapturic acid, and phenylglyoxylic acid), and two chlorinated solvents (trichloroethylene and tetrachloroethylene) were measured in meconium by gas and liquid chromatography, both coupled to tandem mass spectrometry. Associations between the concentration of each chemical and the occurrence of hypospadias were analyzed using exact logistic regressions adjusted for maternal age, educational level, pre-pregnancy body mass index, and alcohol, and tobacco consumption during pregnancy. Results are presented with odds ratios (ORs) and their 95% confidence intervals (CIs). Results: Quantification rates for petroleum and chlorinated solvents or metabolites ranged from 2.2% (for methylhippuric acid) to 77.1% (for trichloroethylene) of the meconium samples. We found a significant association between the quantification of phenylglyoxylic acid (metabolite of styrene and ethylbenzene) in the meconium and a higher risk of hypospadias (OR = 14.2, 95% CI [2.5-138.7]). The risk of hypospadias was non-significantly elevated for most of the other solvents and metabolites. Conclusion: This exploratory study, on a limited number of cases, suggests an association between petroleum solvents and hypospadias. Additional studies are needed to confirm these results and identify the determinants for the presence of these solvents in meconium.

Visual contrast sensitivity in school-age Guadeloupean children exposed to chlordecone.

Recent evidence suggests that prenatal exposure to chlordecone, a persistent organochlorine pesticide that was used intensively in the French West Indies, affects infant neurodevelopment. The aim of the present study was to evaluate the association between prenatal and postnatal chlordecone exposures on visual contrast sensitivity in 285 children aged from 7.1 to 8 years old (mean age = 7.68 ±â€¯0.21 years; sex ratio = 54 % girls) in a Guadeloupean prospective birth cohort (TIMOUN). The Freiburg Visual Acuity and Contrast Test (FrAcT) was used to assess visual contrast sensitivity. Chlordecone concentrations were measured in blood samples at birth (cord blood) and in children at testing time to estimate pre- and postnatal exposure, respectively. Exposures were categorized into three groups and were also log-transformed and considered as continuous variables. Multiple linear regression models were performed on all children taking into account various potential confounders, including maternal characteristics (age, education, intellectual functioning, alcohol and tobacco use during pregnancy). Potential moderation effect of sex was also examined. Results showed that higher cord plasma chlordecone levels were associated with lower contrast sensitivity. Although child chlordecone levels was not associated with the FrAcT, sex-specific stratified analyses revealed significant associations in boys. Associations between postnatal exposure and FrACT scores in girls were null. This study indicates that exposure to chlordecone in utero and during childhood may impair visual contrast sensitivity at school age, particularly in boys.

Prenatal and childhood exposure to chlordecone and sex-typed toy preference of 7-year-old Guadeloupean children.

Chlordecone was used intensively as an insecticide in the French West Indies. Because of its high persistence, the resulting contamination of food and water has led to chronic exposure of the general population as evidenced by its presence in the blood of people of Guadeloupe, in particular in pregnant women and newborns, and in maternal breast milk. Chlordecone is recognized as a reproductive and developmental toxicant, is neurotoxic and carcinogenic in rodents, and is considered as an endocrine-disrupting compound with well-established estrogenic and progestogenic properties both in vitro and in vivo. The question arises of its potential consequences on child neurodevelopment following prenatal and childhood exposure, in particular on behavioral sexual dimorphism in childhood. We followed 116 children from the TIMOUN mother-child cohort study in Guadeloupe, who were examined at age 7. These children were invited to participate in a 7-min structured play session in which they could choose between different toys considered as feminine, masculine, or neutral. The play session was video recorded, and the percentage of the time spent playing with feminine or masculine toys was calculated. We estimated associations between playtime and prenatal exposure to chlordecone (assessed by concentration in cord blood) or childhood exposure (determined from concentrations in child blood obtained at the 7-year follow-up), taking into account confounders and co-exposures to other environmental chemicals. We used a two-group regression model to take into account sex differences in play behavior. Our results do not indicate any modification in sex-typed toy preference among 7-year-old children in relation with either prenatal or childhood exposure to chlordecone.

Epidemiology of Dandy-Walker Malformation in Europe: A EUROCAT Population-Based Registry Study.

BACKGROUND: Dandy-Walker (DW) malformation is a rare and severe congenital anomaly of the posterior fossa affecting the development of the cerebellum and the fourth ventricle. OBJECTIVE: The aim of this study was to investigate the epidemiology of DW malformation, using data from the European population-based registries of congenital anomalies in the European Surveillance of Congenital Anomalies network. METHODS: Anonymous individual data on cases of DW malformation diagnosed in 2002-2015 from 28 registries in 17 countries were included. Prevalence, prenatal detection rate, proportions and types of associated anomalies were estimated. Cases of DW variant were considered and analysed separately. RESULTS: Out of 8,028,454 surveyed births we identified a total of 734 cases, including 562 DW malformation cases and 172 DW variant cases. The overall prevalence of DW malformation was 6.79 per 100,000 births (95% CI 5.79-7.96) with 39.2% livebirths, 4.3% foetal deaths from 20 weeks gestational age, and 56.5% terminations of pregnancy after prenatal diagnosis of foetal anomaly at any gestation (TOPFA). The livebirth prevalence was 2.74 per 100,000 births (95% CI 2.08-3.61). The prenatal detection rate was 87.6%. Two-hundred and seventy-three cases (48.6%) had an isolated cerebral anomaly and 24.2, 19.2 and 5.5% cases were associated with other structural non-cerebral anomalies, chromosomal anomalies and genetic syndromes respectively. The prevalence of DW variant was 2.08 per 100,000 (95% CI 1.39-3.13). CONCLUSIONS: This European population-based study provides the epidemiological profile of DW malformation. All birth outcomes were analysed and TOPFA represented more than half of the cases. About 50% of the cases of DW malformation were associated with other non-cerebral anomalies. Large populations and all birth outcomes are essential in epidemiological studies of rare and severe congenital anomalies.

Epidemiology of achondroplasia: A population-based study in Europe.

Achondroplasia is a rare genetic disorder resulting in short-limb skeletal dysplasia. We present the largest European population-based epidemiological study to date using data provided by the European Surveillance of Congenital Anomalies (EUROCAT) network. All cases of achondroplasia notified to 28 EUROCAT registries (1991-2015) were included in the study. Prevalence, birth outcomes, prenatal diagnosis, associated anomalies, and the impact of paternal and maternal age on de novo achondroplasia were presented. The study population consisted of 434 achondroplasia cases with a prevalence of 3.72 per 100,000 births (95%CIs: 3.14-4.39). There were 350 live births, 82 terminations of pregnancy after prenatal diagnosis, and two fetal deaths. The prenatal detection rate was significantly higher in recent years (71% in 2011-2015 vs. 36% in 1991-1995). Major associated congenital anomalies were present in 10% of cases. About 20% of cases were familial. After adjusting for maternal age, fathers >34 years had a significantly higher risk of having infants with de novo achondroplasia than younger fathers. Prevalence was stable over time, but regional differences were observed. All pregnancy outcomes were included in the prevalence estimate with 80.6% being live born. The study confirmed the increased risk for older fathers of having infants with de novo achondroplasia.

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.

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.

Epidemiology of septo-optic dysplasia with focus on prevalence and maternal age - A EUROCAT study.

Septo-optic nerve dysplasia is a rare congenital anomaly with optic nerve hypoplasia, pituitary hormone deficiencies and midline developmental defects of the brain. The clinical findings are visual impairment, hypopituitarism and developmental delays. The aim of this study was to report prevalence, associated anomalies, maternal age and other epidemiological factors from a large European population based network of congenital anomaly registries (EUROCAT). Data from 29 full member registries for the years 2005-2014 were included, covering 6.4 million births. There were 99 cases with a diagnosis of septo-optic dysplasia. The prevalence of septo-optic dysplasia in Europe was calculated to lie between 1.9 and 2.5 per 100,000 births after adjusting for potential under-reporting in some registries. The prevalence was highest in babies of mothers aged 20-24 years of age and was significantly higher in UK registries compared with other EUROCAT registries (P = 0.021 in the multilevel model) and the additional risk for younger mothers was significantly greater in the UK compared to the rest of Europe (P = 0.027). The majority of septo-optic dysplasia cases were classified as an isolated cerebral anomaly (N = 76, 77%). Forty percent of diagnoses occurred in fetuses with a prenatal diagnosis. The anomaly may not be visible at birth, which is reflected in that 57% of the postnatal diagnoses occurred over 1 month after birth. This is the first population based study to describe the prevalence of septo-optic dysplasia in Europe. Septo-optic dysplasia shares epidemiological patterns with gastroschisis and this strengthens the hypothesis of vascular disruption being an aetiological factor for septo-optic dysplasia.

Prenatal exposure to persistent organic pollutants and organophosphate pesticides, and markers of glucose metabolism at birth.

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

Chlordecone exposure and adverse effects in French West Indies populations.

Chlordecone (Kepone) is an organochlorine insecticide that has been used as insecticide and fungicide. In the French West Indies, Guadeloupe and Martinique, it was intensively applied to banana fields from 1973 to 1993 to control root borers. This pesticide undergoes no significant biotic or abiotic degradation in the environment and is still present in soils where it was applied. It was only in 1999 that health and environmental authorities became aware of the extent of the chlordecone pollution of environmental media, including soils, waterways, and the food chain. Earlier observations and toxicological studies have demonstrated that chlordecone is a reproductive and developmental toxicant, neurotoxic and carcinogenic in rodents, and is an endocrine-disrupting chemical because of its estrogenic properties both in vitro and in vivo. Several surveys have confirmed that the French West Indian population continues to be exposed to this chemical though consumption of contaminated foodstuffs. Here, we report the findings of various epidemiological studies conducted in the French West Indies to assess the impact of environmental exposure to chlordecone on the health of the population.

Exploring educational disparities in risk of preterm delivery: a comparative study of 12 European birth cohorts.

BACKGROUND: An association between education and preterm delivery has been observed in populations across Europe, but differences in methodology limit comparability. We performed a direct cross-cohort comparison of educational disparities in preterm delivery based on individual-level birth cohort data. METHODS: The study included data from 12 European cohorts from Denmark, England, France, Lithuania, the Netherlands, Norway, Italy, Portugal, and Spain. The cohorts included between 2434 and 99 655 pregnancies. The association between maternal education and preterm delivery (22-36 completed weeks of gestation) was reported as risk ratios, risk differences, and slope indexes of inequality with 95% confidence intervals (CIs). RESULTS: Singleton preterm live delivery proportion varied between 3.7% and 7.5%. There were large variations between the cohorts in the distribution of education and maternal characteristics. Nevertheless, there were similar educational differences in risk of preterm delivery in 8 of the 12 cohorts with slope index of inequality varying between 2.2 [95% CI 1.1, 3.3] and 4.0 [95% CI 1.4, 6.6] excess preterm deliveries per 100 singleton deliveries among the educationally most disadvantaged, and risk ratio between the lowest and highest education category varying from 1.4 [95% CI 1.1, 1.8] to 1.9 [95% CI 1.2, 3.1]. No associations were found in the last four cohorts. CONCLUSIONS: Educational disparities in preterm delivery were found all over Europe. Despite differences in the distributions of education and preterm delivery, the results were remarkably similar across the cohorts. For those few cohorts that did not follow the pattern, study and country characteristics did not explain the differences.

Survival and morbidity of preterm children born at 22 through 34 weeks' gestation in France in 2011: results of the EPIPAGE-2 cohort study.

IMPORTANCE: Up-to-date estimates of the health outcomes of preterm children are needed for assessing perinatal care, informing parents, making decisions about care, and providing evidence for clinical guidelines. OBJECTIVES: To determine survival and neonatal morbidity of infants born from 22 through 34 completed weeks' gestation in France in 2011 and compare these outcomes with a comparable cohort in 1997. DESIGN, SETTING, AND PARTICIPANTS: The EPIPAGE-2 study is a national, prospective, population-based cohort study conducted in all maternity and neonatal units in France in 2011. A total of 2205 births (stillbirths and live births) and terminations of pregnancy at 22 through 26 weeks' gestation, 3257 at 27 through 31 weeks, and 1234 at 32 through 34 weeks were studied. Cohort data were collected from January 1 through December 31, 1997, and from March 28 through December 31, 2011. Analyses for 1997 were run for the entire year and then separately for April to December; the rates for survival and morbidities did not differ. Data are therefore presented for the whole year in 1997 and the 8-month and 6-month periods in 2011. MAIN OUTCOMES AND MEASURES: Survival to discharge and survival without any of the following adverse outcomes: grade III or IV intraventricular hemorrhage, cystic periventricular leukomalacia, severe bronchopulmonary dysplasia, retinopathy of prematurity (stage 3 or higher), or necrotizing enterocolitis (stages 2-3). RESULTS: A total of 0.7% of infants born before 24 weeks' gestation survived to discharge: 31.2% of those born at 24 weeks, 59.1% at 25 weeks, and 75.3% at 26 weeks. Survival rates were 93.6% at 27 through 31 weeks and 98.9% at 32 through 34 weeks. Infants discharged home without severe neonatal morbidity represented 0% at 23 weeks, 11.6% at 24 weeks, 30.0% at 25 weeks, 47.5% at 26 weeks, 81.3% at 27 through 31 weeks, and 96.8% at 32 through 34 weeks. Compared with 1997, the proportion of infants surviving without severe morbidity in 2011 increased by 14.4% (P < .001) at 25 through 29 weeks and 6% (P < .001) at 30 through 31 weeks but did not change appreciably for those born at less than 25 weeks. The rates of antenatal corticosteroid use, induced preterm deliveries, cesarean deliveries, and surfactant use increased significantly in all gestational-age groups, except at 22 through 23 weeks. CONCLUSIONS AND RELEVANCE: The substantial improvement in survival in France for newborns born at 25 through 31 weeks' gestation was accompanied by an important reduction in severe morbidity, but survival remained rare before 25 weeks. Although improvement in survival at extremely low gestational age may be possible, its effect on long-term outcomes requires further studies. The long-term results of the EPIPAGE-2 study will be informative in this regard.

Analysis of BTEX and chlorinated solvents in meconium by headspace-solid-phase microextraction gas chromatography coupled with mass spectrometry.

Meconium is the earliest stool of newborns, and is a complex matrix that reflects the degree of exposure of the fetus to xenobiotics. To investigate fetal exposure to volatile organic compounds, an analytical method was developed to identify and quantify BTEX (benzene, toluene, ethylbenzene, and o,m,p-xylene) and two chlorinated solvents (trichloroethylene and tetrachloroethylene) in meconium. Headspace-solid-phase microextraction coupled with gas chromatography-mass spectrometry was selected because it is simple, sensitive, can be automated, and requires no extensive sample preparation. Several extraction variables were optimized (fiber type, incubation time, temperature of fiber, and use of salt). Because meconium is a complex matrix, quantification by SPME was considered carefully because of potential interference, for example competitive adsorption. Calibration in water was compared with calibration in meconium using external and internal methods (with isotope-labeled compounds). In meconium, limits of quantification were determined to be in the range 0.064-0.096 ng g(-1) for the investigated compounds. All target compounds were determined in "real-case" meconium samples.

Exposure to an organochlorine pesticide (chlordecone) and development of 18-month-old infants.

Chlordecone is a persistent organochlorine pesticide that was used in the French West Indies until the early 1990s for banana weevil borer control. Human exposure to this chemical in this area still occurs nowadays due to consumption of contaminated food. Although adverse effects on neurodevelopment, including tremors and memory deficits, have been documented in experimental studies conducted with rodents exposed during the gestational and neonatal periods, no study has been conducted yet to determine if chlordecone alters child development. This study examines the relation of gestational and postnatal exposure to chlordecone to infant development at 18 months of age in a birth-cohort of Guadeloupean children. In a prospective longitudinal study conducted in Guadeloupe (Timoun mother-child cohort study), exposure to chlordecone was measured at birth from an umbilical cord blood sample (n=141) and from a breast milk sample collected at 3 months postpartum (n=75). Toddlers were assessed using an adapted version of the Ages and Stages Questionnaire. Higher chlordecone concentrations in cord blood were associated with poorer fine motor scores. When analyses were conducted separately for boys and girls, this effect was only observed among boys. These results suggest that prenatal exposure to chlordecone is associated with specific impairments in fine motor function in boys, and add to the growing evidence that exposure to organochlorine pesticides early in life impairs child development.

Occupational solvent exposure during pregnancy and child behaviour at age 2.

OBJECTIVES: Many women who work during pregnancy are occupationally exposed to toxicants. The developing central nervous system is highly vulnerable to neurotoxicants such as solvents. Although the neurotoxicity of solvents to adults is well established, very few studies have examined their effects on children's behaviour following prenatal exposure. METHODS: Women from the Perturbateurs endocriniens: Étude Longitudinale sur les Anomalies de la Grossesse, l'Infertilité et l'Enfance (PELAGIE) mother-child cohort (including 3005 working women) were recruited in Brittany (France) between 2002 and 2006, at the beginning of pregnancy, to assess occupational exposure to solvents at that time. Child behaviour was documented at age 2 by mothers (n=1278) assessing components of attention deficit/hyperactivity, aggression, opposition and emotionality. We used a multiple linear regression analysis to evaluate the association between occupational solvent exposure and children's behaviour. Complementary sensitivity analyses allowed us to handle missing data, due mostly to attrition. RESULTS: 20% of women reported occasional exposure and 31% regular exposure to solvents. Children prenatally exposed were more likely to have higher scores of attention deficit/hyperactivity and aggression, and dose-response relations were observed. CONCLUSIONS: The dose-response effect and the high prevalence of children potentially exposed to solvents from their mother's workplace exposure underline the public health relevance of this result. Our results should be replicated in further studies designed to identify which solvents are most deleterious and to assess child behaviour at school age.

Urinary biomarkers of prenatal atrazine exposure and adverse birth outcomes in the PELAGIE birth cohort.

BACKGROUND: Despite evidence of atrazine toxicity in developing organisms from experimental studies, few studies--and fewer epidemiologic investigations--have examined the potential effects of prenatal exposure. OBJECTIVES: We assessed the association between adverse birth outcomes and urinary biomarkers of prenatal atrazine exposure, while taking into account exposures to other herbicides used on corn crops (simazine, alachlor, metolachlor, and acetochlor). METHODS: This study used a case-cohort design nested in a prospective birth cohort conducted in the Brittany region of France from 2002 through 2006. We collected maternal urine samples to examine pesticide exposure biomarkers before the 19th week of gestation. RESULTS: We found quantifiable levels of atrazine or atrazine mercapturate in urine samples from 5.5% of 579 pregnant women, and dealkylated and identified hydroxylated triazine metabolites in 20% and 40% of samples, respectively. The presence versus absence of quantifiable levels of atrazine or a specific atrazine metabolite was associated with fetal growth restriction [odds ratio (OR) = 1.5; 95% confidence interval (CI), 1.0-2.2] and small head circumference for sex and gestational age (OR = 1.7; 95% CI, 1.0-2.7). Associations with major congenital anomalies were not evident with atrazine or its specific metabolites. Head circumference was inversely associated with the presence of quantifiable urinary metolachlor. CONCLUSIONS: This study is the first to assess associations of birth outcomes with multiple urinary biomarkers of exposure to triazine and chloroacetanilide herbicides. Evidence of associations with adverse birth outcomes raises particular concerns for countries where atrazine is still in use.