Search

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

Objectives To describe urine levels of metabolites of glycol ethers and chlorinated solvents in a sample of pregnant women from the general population, to study their occupational and non-occupational determinants and to compare them with the results of indirect assessment methods of solvent exposure. Methods A sample of 451 pregnant women was randomly selected from a general population cohort. At inclusion, the women in this sample completed a self-administered questionnaire about their social and medical characteristics, occupation and exposure to different products at work and in non-occupational activities. Occupational exposure to solvents was assessed from the woman's self-report and from a job-exposure matrix. Eight alkoxycarboxylic acids and trichloroacetic acid and trichloroethanol were measured with chromatography in urine samples collected at inclusion. Associations between metabolite levels and job titles, exposure to products used at work, and solvent exposure were studied. Results The different glycol ether metabolites were detected in 5.3%-96.4% of the urine samples, trichloroacetic acid in 6.4% and trichloroethanol in 5.5%. Nurses had butoxyacetic acid and phenoxyacetic acid in their urine most often, whereas methoxyethoxyacetic acid was the most frequent among nursing aides. Among cleaners, ethoxyacetic acid and ethoxyethoxyacetic acid were the most frequent. The occupation of hairdresser was associated with urinary excretion of ethoxyacetic acid, ethoxyethoxyacetic acid, butoxyacetic acid and phenoxyacetic acid. Among the women classified as exposed to solvents, the agents identified most often were ethoxyacetic acid, ethoxy-ethoxyacetic acid, butoxyacetic acid, phenoxyacetic acid, trichloroacetic acid and trichloroethanol. Ethoxyethoxyacetic acid was the only metabolite associated with non-occupational exposure. Conclusions Metabolites of glycol ethers and chlorinated solvents were present at low levels in the urine of pregnant women. Most metabolites were associated with occupational exposure. [ABSTRACT FROM AUTHOR]

Abstract Background Pesticide use is widespread in agriculture. Several studies have shown that pesticides used in agricultural fields can contaminate the domestic environment and thus be an important source of pesticide exposure of populations residing nearby. Epidemiological studies that have examined the health effects of in utero pesticide exposure from residence near agricultural activities suggest adverse effects, but the results are inconsistent. Our purpose was to investigate the effect on intrauterine growth of such exposure due to agricultural activities in the residential municipality. Methods A prospective birth cohort recruited 3421 pregnant women in a French agricultural region (Brittany, 2002-2006) through gynecologists, ultrasonographers, and maternity hospitals during routine prenatal care visits before 19 weeks of gestation. The national agricultural census in 2000 provided the percentages of the municipality area devoted to cultivation of corn, wheat, colza, peas, potatoes, and fresh vegetables. Results Birth weight and the risk of fetal growth restriction were not associated with agricultural activities in the municipality of residence in early pregnancy. Children whose mother lived in a municipality where peas were grown had a smaller head circumference at birth than those in municipalities not growing peas (-0.2 cm, p = 0.0002). Head circumference also tended to be lower when wheat was grown, but not to a statistically significant degree (p-trend = 0.10). Risk of an infant with a small head circumference was higher for mothers living in a municipality where peas (OR = 2.2; 95% CI = 1.2-3.6) or potatoes (OR = 1.5; 95% CI = 0.9-2.4) were grown. Conclusions Agricultural activities in the municipality of residence may have negative effects on cranial growth. Cultivation of pea crops and, to a lesser degree, potato and wheat crops, may negatively affect head circumference. Insecticides, including organophosphate insecticides, were applied to most of the area devoted to pea and potato crops; this was less true for corn and wheat crops. These results must be interpreted in light of the study's limitations, in particular, the scale at which we could assess pesticide exposure.

Abstract Background Recommendations about risks and benefits of seafood intake during pregnancy have been published in the last decade, but the specific health effects of the different categories of seafood remain unknown. Fish and shellfish may differ according to their fatty acid content and their concentration of chemical pollutants and toxins. Not taking these particularities into account may result in underestimating of both the positive and negative effects of seafood on birth outcomes and partly explains inconsistent results on the subject. Methods In the PELAGIE cohort study, including 2398 pregnant women from Brittany, we fit multiple linear and logistic regression models to examine associations of fish (salt-water fish only) and shellfish intake before pregnancy with length of gestation, birthweight, and risks of preterm births, low birthweight or small-for-gestational-age (SGA) babies. Results When fish and shellfish consumptions were considered simultaneously, we observed a decrease in the risk of SGA birth with increasing frequency of fish intake: OR = 0.57 (95%CI: 0.31 to 1.05) for women eating fish twice a week or more compared with those eating it less than once a month. The risk of SGA birth was significantly higher among women eating shellfish twice a week or more than among those eating it less than once a month: OR = 2.14 (95%CI: 1.13 to 4.07). Each additional monthly meal including fish was significantly related to an increase in gestational length of 0.02 week (95%CI: 0.002 to 0.035). No association was observed with birthweight or preterm birth. Conclusion These results suggest that different categories of seafood may be differently associated with birth outcomes, fish consumption with increased length of gestation and shellfish consumption with decreased fetal growth.

Background: Congenital ocular anomalies (COA) are among the most common causes of visual impairment in children in high-income countries. The aim of the study is to describe the prevalence of the various COA recorded in European population-based registries of CA (EUROCAT) participating in the EUROmediCAT consortium., Methods: Data from 19 EUROmediCAT registries and one healthcare database (EFEMERIS) were included in this descriptive epidemiological study. Cases of COA included live births, FD from 20 weeks gestational age (GA), and termination of pregnancy for fetal anomaly., Results: The prevalence of total COA was 3.47/10,000 births (95% CI [3.61-3.82]), ranging from 1.41 to 13.46/10,000 depending on the registry. Among COA cases, congenital lens anomalies were the most frequent anomalies (31%), of which over half were single ocular anomalies (presenting with only one ocular anomaly). An/microphthalmia was the second most frequent COA (24%) of which three-quarters were multiply malformed (associated to extraocular major anomalies). Among single COA cases, 58 were prenatally diagnosed (4%), of which, 58% were diagnosed in the second trimester. Known genetic causes of COA explained 2.5%-25% of COA depending on their class., Conclusions: This is the first European study describing COA. The detailed prevalence data offered in this study could improve screening and early diagnosis of different classes of COA. As COA are rare, epidemiological surveillance of large populations and accurate clinical descriptions are essential., (© 2024 The Author(s). Birth Defects Research published by Wiley Periodicals LLC.)

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., (© 2024. The Author(s).)

Although the ovarian reserve is constituted in utero, the literature on the effects of persistent organic pollutants (POPs) during this vulnerable period on the ovarian reserve later in life is limited. We investigated whether cord blood concentrations of POPs were associated with decreased anti-Müllerian hormone (AMH, a marker of the ovarian reserve) levels in girls at the age of 12. We included 239 girls from the French mother-child PELAGIE cohort. POP concentrations of 14 organochlorine pesticides, 17 polychlorinated biphenyls (PCBs), 5 polybrominated diphenyl ethers, and 9 per-polyfluoroalkyl substances were measured on cord blood sampled at birth. During a follow-up study at 12 years old, blood samples were collected to measure AMH levels. Single-exposure associations were examined with multivariable linear regression models adjusted a priori for potential confounders. Stratification on menarche status was also performed. Mixture effects were investigated using quantile g-computation and Bayesian kernel machine regression. Overall, 16 POPs were measured in at least 30% of samples. No significant associations were found in multivariable linear regressions, except for the third tercile of exposure to PCB 180 which was statistically significantly associated with an increase in AMH levels at 12 years old (Tercile 2 v. Tercile 1: 0.13 ng/mL, 95% CI = -0.29, 0.56; Tercile 3 v. Tercile 1: 0.51 ng/mL, 95% CI = 0.02, 0.99). Additionally, in post-menarcheal girls (N = 104) only, the second tercile of p,p'-DDE was statistically significantly associated with decreased AMH levels at 12 years old (Tercile 2 v. Tercile 1: -0.61 ng/mL, 95% CI = -1.16, -0.05, Tercile 3 v. Tercile 1: 0.02 ng/mL, 95% CI = -0.51, 0.54). Both mixture models returned null associations. Despite the limited associations observed in this study, we recommend exploring these associations in larger mother-child cohorts and at older ages., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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 (β log2  = 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 (β log2  = 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 (β log2  = -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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Many human teratogens are associated with a spectrum of congenital anomalies rather than a single defect, and therefore the identification of congenital anomalies occurring together more frequently than expected may improve the detection of teratogens. Thirty-two EUROCAT congenital anomaly registries covering 6,599,765 births provided 123,566 cases with one or more major congenital anomalies (excluding chromosomal and genetic syndromes) for the birth years 2008-2016. The EUROCAT multiple congenital anomaly algorithm identified 8804 cases with two or more major congenital anomalies in different organ systems, that were not recognized as part of a syndrome or sequence. For each pair of anomalies, the odds of a case having both anomalies relative to having only one anomaly was calculated and the p value was estimated using a two-sided Fisher's exact test. The Benjamini-Hochberg procedure adjusted p values to control the false discovery rate and pairs of anomalies with adjusted p values < 0.05 were identified. A total of 1386 combinations of two anomalies were analyzed. Out of the 31 statistically significant positive associations identified, 20 were found to be known associations or sequences already described in the literature and 11 were considered "potential new associations" by the EUROCAT Coding and Classification Committee. After a review of the literature and a detailed examination of the individual cases with the anomaly pairs, six pairs remained classified as new associations. In summary, systematically searching for congenital anomalies occurring together more frequently than expected using the EUROCAT database is worthwhile and has identified six new associations that merit further investigation., (© 2023. The Author(s).)

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., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Per- and polyfluoroalkyl substances (PFAS) are chemical substances spread throughout the environment worldwide. Exposure during pregnancy represents a specific window of vulnerability for child health., Objective: Our objective was to assess the impact of prenatal exposure to multiple PFAS on emotional and behavioral functions in 12-y-old children., Method: In the PELAGIE mother-child cohort (France), prenatal exposure to nine PFAS was measured from concentrations in cord serum samples. Behavior was assessed at age 12 y using the parent-reported Strengths and Difficulties Questionnaire (SDQ) and the self-reported Dominic Interactive for Adolescents (DIA) for 444 children. Associations were estimated using negative binomial models for each PFAS. Bayesian kernel machine regression (BKMR) models were performed to assess the exposure mixture effect on children's behavior., Results: In our study population, 73% of mothers had spent more than 12 y in education. Higher scores on SDQ externalizing subscale were observed with increasing cord-serum concentration of perfluorooctanoic acid (PFOA) and perfluorononanoic acid (PFNA) [adjusted mean ratio ( aMR ) = 1.18 , 95% confidence interval (CI): 1.03, 1.34, and aMR = 1.14 (95% CI: 1.00, 1.29) for every doubling of concentration, respectively]. Results for the hyperactivity score were similar [ aMR = 1.20 (95% CI: 1.04, 1.40) and aMR = 1.18 (95% CI: 1.02, 1.36), respectively]. With regard to major depressive disorder and internalizing subscales, perfluorodecanoic acid (PFDA) was associated with higher self-reported DIA scores [ aMR = 1.14 (95% CI: 1.01, 1.27) and aMR = 1.11 (95% CI: 1.02, 1.21), respectively]. In terms of the anxiety subscale, PFDA and PFNA were associated with higher scores [ aMR = 1.11 (95% CI: 1.02, 1.21) and aMR = 1.10 (95% CI: 1.01, 1.19), respectively]. Concurrent increases in the PFAS concentrations included in the BKMR models showed no change in the SDQ externalizing and DIA internalizing subscales scores., Conclusion: Prenatal exposure to PFNA and PFOA were associated with increasing scores for measures of externalizing behaviors, specifically hyperactivity. We also identified associations between PFNA and PFDA prenatal exposure levels and increasing scores related to internalizing behaviors (general anxiety and major depressive disorder), which adds to the as yet sparse literature examining the links between prenatal exposure to PFAS and internalizing disorders. https://doi.org/10.1289/EHP12540.

Aim: To describe the circumstances, causes and timing of death in extremely preterm infants., Methods: We included from the EPIPAGE-2 study infants born at 24-26 weeks in 2011 admitted to neonatal intensive care units (NICU). Vital status and circumstances of death were used to define three groups of infants: alive at discharge, death with or without withholding or withdrawing life-sustaining treatment (WWLST). The main cause of death was classified as respiratory disease, necrotizing enterocolitis, infection, central nervous system (CNS) injury, other or unknown., Results: Among 768 infants admitted to NICU, 224 died among which 89 died without WWLST and 135 with WWLST. The main causes of death were respiratory disease (38%), CNS injury (30%) and infection (12%). Among the infants who died with WWLST, CNS injury was the main cause of death (47%), whereas respiratory disease (56%) and infection (20%) were the main causes in case of death without WWLST. Half (51%) of all deaths occurred within the first 7 days of life, and 35% occurred within 8 and 28 days., Conclusion: The death of extremely preterm infants in NICU is a complex phenomenon in which the circumstances and causes of death are intertwined., (© 2023 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Background: Several studies have reported that prenatal exposure to some persistent organic pollutants (POPs) is associated with higher adiposity in childhood. Few studies have assessed whether this finding persists into adolescence, and few have considered exposure to POPs as a mixture. This study aims to assess the association between prenatal exposure to multiple POPs and adiposity markers and blood pressure in preadolescents., Methods: This study included 1667 mother-child pairs enrolled in the PELAGIE (France) and the INMA (Spain) mother-child cohorts. Three polychlorobiphenyls (PCB 138, 153 and 180, treated as a sum of PCBs) and three organochlorine pesticides (p,p'-Dichlorodiphenyldichloroethylene [p,p'-DDE], β-hexachlorocyclohexane [β-HCH], and hexachlorobenzene [HCB]) were assessed in maternal or cord serum. Body mass index z-score (zBMI), abdominal obesity (waist-to-height ratio > 0.5), percentage of fat mass, and blood pressure (mmHg) were measured at around 12 years of age. Single-exposure associations were studied using linear or logistic regressions, and the POP mixture effect was evaluated using quantile G-computation (qgComp) and Bayesian Kernel Machine Regression (BKMR). All models were adjusted for potential confounders and performed for boys and girls together and separately., Results: Prenatal exposure to the POP mixture was associated with higher zBMI (beta [95 % CI] of the qgComp = 0.15 [0.07; 0.24]) and percentage of fat mass (0.83 [0.31; 1.35]), with no evidence of sex-specific association. These mixture effects were also statistically significant using BKMR. These associations were driven mainly by exposure to HCB and, to a lesser extent, to β-HCH. In addition, the single-exposure models showed an association between β-HCH and p,p'-DDE and higher systolic blood pressure, especially in girls (p,p'-DDE for girls = 1.00 [0.15; 1.86]). No significant associations were found for PCBs., Conclusion: This study suggests that prenatal exposure to POPs, particularly organochlorine pesticides, remains associated with unfavorable cardiometabolic health up to the age of 12., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Amniotic band syndrome (ABS) and limb body wall complex (LBWC) have an overlapping phenotype of multiple congenital anomalies and their etiology is unknown. We aimed to determine the prevalence of ABS and LBWC in Europe from 1980 to 2019 and to describe the spectrum of congenital anomalies. In addition, we investigated maternal age and multiple birth as possible risk factors for the occurrence of ABS and LBWC. We used data from the European surveillance of congenital anomalies (EUROCAT) network including data from 30 registries over 1980-2019. We included all pregnancy outcomes, including live births, stillbirths, and terminations of pregnancy for fetal anomalies. ABS and LBWC cases were extracted from the central EUROCAT database using coding information responses from the registries. In total, 866 ABS cases and 451 LBWC cases were included in this study. The mean prevalence was 0.53/10,000 births for ABS and 0.34/10,000 births for LBWC during the 40 years. Prevalence of both ABS and LBWC was lower in the 1980s and higher in the United Kingdom. Limb anomalies and neural tube defects were commonly seen in ABS, whereas in LBWC abdominal and thoracic wall defects and limb anomalies were most prevalent. Twinning was confirmed as a risk factor for both ABS and LBWC. This study includes the largest cohort of ABS and LBWC cases ever reported over a large time period using standardized EUROCAT data. Prevalence, clinical characteristics, and the phenotypic spectrum are described, and twinning is confirmed as a risk factor., (© 2022 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.)

Background: Evidence on the direction and strength of association between maternal age and the prevalence of congenital heart defects (CHD) in different age group categories is conflicting. Some studies have illustrated different trends with an increase in prevalence in younger and older age groups while other studies have reported a linear relationship. Given the increase in maternal age over recent years, it is important to study the CHD prevalence by maternal age., Objectives: To examine the association between maternal age and the prevalence of CHD in Europe between 1995 and 2015 using population-based data from 24 registries belonging to the European Surveillance of Congenital Anomalies (EUROCAT) network., Methods: Associations over time of all nonsyndromic CHD according to maternal age category and for three CHD severity groupings (severity group I: very severe; severity group II: severe; severity group III: less severe) were examined using Bayesian multilevel Poisson regression modeling. Further subgroup analyses were undertaken within four maternal age-bands: ≤24, 25-29, 30-34 and 35-44 years. Descriptive summaries are also presented., Results: There were 51,608 nonsyndromic CHD cases in Europe over the 20-year study period. Total prevalence for all CHD combined was increased for younger mothers (≤24 years) and for mothers 35-44 years of age when compared with mothers aged 25-29 years (reference group) (IRR: 1.05, 95% CI: 1.02, 1.07). The total prevalence was increased for severity group I (very severe) only for younger mothers compared to those aged 25-29 years (IRR: 1.14, 95% CI: 1.04, 1.23). We found an increased prevalence of the following CHD subtypes: double outlet right ventricle (IRR:1.33, 95% CI: 1.09, 1.60), hypoplastic left heart syndrome (IRR: 1.18, 95% CI: 1.05, 1.32), hypoplastic right heart syndrome (IRR: 1.41, 95% CI: 1.05, 1.84), atrioventricular septal defect (IRR: 1.15, 95% CI: 1.01, 1.32), coarctation of aorta (IRR: 1.15, 95% CI: 1.03, 1.28) and atrial septal defect (IRR: 1.08, 95% CI: 1.02, 1.13). For older mothers (35-44 years) compared to the reference category, we observed an increased risk in the prevalence for severity group II (IRR: 1.09, 95% CI: 1.03, 1.14), severity group III (IRR: 1.05, 95% CI: 1.01, 1.08) and an increased prevalence of the CHD subtypes: Pulmonary valve stenosis (IRR: 1.22, 95% CI: 1.09, 1.34), ASD (IRR: 1.07, 95% CI: 1.02, 1.13), CoA (IRR: 1.18, 95% CI: 1.06, 1.32) and Tetralogy of Fallot (IRR: 1.14, 95% CI: 1.01, 1.28). Finally, for all age categories compared to the reference category, different associations of ASD and an increased prevalence of CoA was also observed., Conclusions: Based on data for cases of CHD from 24 European population-based registries, evidence of a positive association between maternal age and the total prevalence of CHD for younger (≤24 years old) and older (35-44 years old) mothers was observed. The results suggest that young maternal age (≤24 years old) is a factor associated with severe CHD phenotypes while a positive association between advanced maternal age (35-44 years old) and mild CHD phenotypes was observed., (© 2023 The Authors. Birth Defects Research published by Wiley Periodicals LLC.)

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., (© 2022 European Academy of Dermatology and Venereology.)

Background: Chlordecone is a highly persistent organochlorine insecticide that was intensively used in banana fields in the French West Indies, resulting in a widespread contamination. Neurotoxicity of acute exposures in adults is well recognized, and empirical data suggests that prenatal exposure affects visual and fine motor developments during infancy and childhood, with greater susceptibility in boys., Objective: To assess the associations between pre- and postnatal exposures to chlordecone and cognitive and behavioral functions in school-aged children from Guadeloupe., Methods: We examined 576 children from the TIMOUN mother-child cohort in Guadeloupe at 7 years of age. Concentrations of chlordecone and other environmental contaminants were measured in cord- and children's blood at age 7 years. Cognitive abilities of children were assessed with the Wechsler Intelligence Scale for Children-IV (WISC-IV), and externalizing and internalizing problem behaviors documented with the Strengths and Difficulties Questionnaire (SDQ) completed by the child's mother. We estimated covariate-adjusted associations between cord- and 7-years chlordecone concentrations and child outcomes using structural equations modeling, and tested effect modification by sex., Results: Geometric means of blood chlordecone concentrations were 0.13 µg/L in cord blood and 0.06 µg/L in children's blood at age 7 years. A twofold increase in cord blood concentrations was associated with 0.05 standard deviation (SD) (95% Confidence Interval [CI]: 0.0, 0.10) higher internalizing problem scores, whereas 7-years chlordecone concentrations were associated with lower Full-Scale IQ scores (FSIQ) and greater externalized behavioral problem scores. A twofold increase in 7-year chlordecone concentrations was associated with a decrease of 0.67 point (95% CI: -1.13, -0.22) on FSIQ and an increase of 0.04 SD (95% CI: 0.0, 0.07) on externalizing problems. These associations with Cognitive abilities were driven by decreases in perceptive reasoning, working memory and verbal comprehension. Associations between 7-year exposure and perceptive reasoning, working memory, and the FSIQ were stronger in boys, whereas cord blood and child blood associations with internalizing problems were stronger in girls., Conclusions: These results suggests that cognitive abilities and externalizing behavior problems at school age are impaired by childhood, but not in utero, exposure to chlordecone, and that prenatal exposure is related to greater internalizing behavioral problems., (© 2023. The Author(s).)

Introduction: Polychlorobiphenyls (PCBs), organochlorine pesticides (OCPs), and per- and polyfluoroalkyl substances (PFASs) are persistent organic pollutants (POPs) having numerous toxicological properties, including thyroid endocrine disruption. Our aim was to assess the impact of POPs on thyroid hormones among 12-year-old children, while taking puberty into consideration., Methods: Exposure to 7 PCBs, 4 OCPs, and 6 PFASs (in µg/L), and free tri-iodothyronine (fT3, pg/mL), free thyroxine (fT4, ng/dL), and thyroid-stimulating hormones (TSH, mIU/L) were assessed through blood-serum measurements at age 12 years in 249 boys and 227 girls of the PELAGIE mother-child cohort (France). Pubertal status was clinically rated using the Tanner stages. For each POP, associations were estimated using linear regression, adjusted for potential confounders., Results: Among boys, hexachlorobenzene and perfluorodecanoic acid were associated with decreased fT3 (log-scale; β [95% confidence interval] = -0.07 [-0.12,-0.02] and β = -0.03 [-0.06,-0.00], respectively). Intermediate levels of perfluorohexanesulfonic acid (PFHxS) and PCB180 were associated, respectively, with increased and decreased fT4. After stratification on pubertal status, PCBs and OCPs were associated with decreased TSH only in the more advanced Tanner stages (3-5) and with decreased fT3 among early Tanner stages (1-2). Among girls, PFHxS was associated with decreased TSH (log-scale; β = -0.15 [-0.29,-0.00]), and perfluorooctanoic acid was associated with decreased fT3 (β2nd&#95;tercile = -0.06 [-0.10,-0.03] and β3rd&#95;tercile = -0.04 [-0.08,-0.00], versus. 1st tercile)., Discussion: This cross-sectional study highlights associations between some POPs and thyroid function disruption, which appears consistent with the literature. Considering that the associations were sex-specific and moderated by pubertal status in boys, complex endocrine interactions are likely involved., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Background: The total prevalence of congenital heart defects (CHDs) varies by populations and over time. Studies that examine trends in the prevalence of CHD in different regions may shed light on our understanding of the occurrence of CHD and the impact of different risk factors., Objectives: To examine trends in total and live birth prevalence of nonsyndromic CHD in Europe between the years 2008 and 2015 and to investigate if the decreasing trend reported by previous studies is continuing., Methods: Cases of CHD delivered between January 1, 2008 and December 31, 2015 notified to 25 population-based EUROCAT (European Surveillance of Congenital Anomalies) registries in 14 countries, formed the population-based case-series. Prevalence (total/live) rates and 95% confidence intervals were calculated as the number of cases per 10,000 births (live and stillbirths). Time trends in prevalence of all nonsyndromic CHDs and for three CHD severity groups (very severe, severe, and less severe) were plotted using a Poisson regression multilevel approach., Results: The total prevalence of nonsyndromic CHD was 57.1 per 10,000 births (live births and stillbirths) for the 8-year period and remained stable across the three CHD severity groups while the live birth prevalence was 60.2 per 10,000 births. There was considerable variation in the reported total CHD prevalence and the direction of trends by registry. A decreasing prevalence of CHD was observed for the Norway and England/Wales registries, whereas the CHD prevalence increased for registries in Italy and Croatia., Conclusions: The total prevalence of CHD in Europe between the years 2008 and 2015 remained stable for all CHD and across the three CHD severity groups. The decreasing trend reported by previous studies has not continued. However, we found significant differences in the total and live birth prevalence by registry., (© 2022 The Authors. Birth Defects Research published by Wiley Periodicals LLC.)

Background: Younger mothers are at a greater risk of having a pregnancy with gastroschisis and the risk is higher in the United Kingdom than other European countries. Gastroschisis is thought to be a vascular disruption anomaly and the aim of this study was to analyze the prevalence of other possible vascular disruption anomalies to determine whether both the younger maternal age and the UK associations also occur with these anomalies., Methods: All pregnancies with anomalies considered potentially due to vascular disruption from January 1, 2005 to December 31, 2017 from 26 European population-based congenital anomaly registries who were members of EUROCAT were analyzed. Multilevel models were used to allow for differences between registries when analyzing associations with maternal age, year of birth and whether the registry was in the United Kingdom., Results: There were 5,220 cases with potential vascular disruption anomalies, excluding chromosomal and genetic conditions, with a prevalence of 8.85 per 10,000 births in the United Kingdom and 5.44 in the other European countries. The prevalence per 10,000 births of gastroschisis (4.45 vs. 1.56) and congenital constriction bands (0.83 vs. 0.42) was significantly higher in the United Kingdom, even after adjusting for maternal age. However, transverse limb reduction defects had a similar prevalence (2.16 vs. 2.14 per 10,000). The expected increased prevalence in younger mothers was observed for vascular disruption anomalies overall and for the individual anomalies: gastroschisis and congenital constriction bands., Conclusion: Vascular disruption anomalies that had an increased risk for younger mothers (such as gastroschisis) had a higher maternal age standardized prevalence in the United Kingdom, while vascular disruption anomalies with weaker associations with younger mothers (such as transverse limb reduction defects) did not have an increased prevalence in the United Kingdom, which may indicate a different etiology for these anomalies., (© 2022 The Authors. Birth Defects Research published by Wiley Periodicals LLC.)

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., (Copyright © 2022 Elsevier Inc. All rights reserved.)

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., (© 2022. The Author(s).)

Background: Chlordecone is an organochlorine that was largely used as an insecticide to control a species of root borers, the Banana weevil (Cosmopolites sordidus), in the French West Indies, Guadeloupe and Martinique. Its molecules have been shown to be very persistent in the environment as pollution in soils leading to contamination of water sources and foodstuff will last for several decades. Our team previously reported associations between prenatal chlordecone exposure and poorer fine motor development at two points in time during infancy., Objective: To document whether effects of prenatal exposure to chlordecone previously reported persists until middle-childhood, and whether deleterious effects are observed in domain of visual processing. Associations with postnatal exposure and sex-specific vulnerabilities were also investigated., Methods: We examined 410 children from the TIMOUN mother-child cohort in Guadeloupe at 7 years of age. Concentrations of chlordecone and other environmental contaminants were measured in cord- and children's blood at age 7 years. Fine motor function was assessed using the Bruininks Oseretsky Test of Motor Proficiency Second Edition (BOT-2). The Computerized Adaptive Testing System (CATSYS) was used to evaluated postural hand tremor, while non-verbal visuospatial processing was measured using the Stanford Binet copying (S-B copying) test. We used adjusted multiple linear regressions to test the relationship between children's scores and both continuous and categorical blood chlordecone concentrations, adding child sex as a moderator in continuous models., Results: Cord chlordecone concentrations are associated with a regular frequency pattern of subtle hand tremors in both hands, and not related to visual processing and fine motor precision. Chlordecone concentrations in blood sample collected at testing time are associated with poorer visual processing when copying geometric figures, but not significantly related to poorer fine movement precision in tasks requiring pencil, scissors and paper. No sex-specific vulnerability was reported in any of the outcomes., Conclusions: These results at school aged expand those previously reported in the same cohort during infancy at age 7- and 18 months, and corroborate the negative effects of chlordecone exposure on fine motor function in absence of intoxication. Our results support the need to continue public health efforts aimed at reducing exposure especially among women of child bearing age and young children., (Copyright © 2021 Elsevier B.V. All rights reserved.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ayhan, Rouget, Giton, Costet, Michineau, Monfort, Thomé, Kadhel, Cordier, Oliva and Multigner.)

Background: Pierre Robin sequence (PRS) is a rare congenital anomaly. Respiratory disorders and feeding difficulties represent the main burden., Objective: The aim of this study was to investigate the epidemiology of PRS using a cohort of cases from EUROCAT, the European network of population-based registries of congenital anomalies., Methods: We analysed cases of PRS born in the period 1998-2017 collected by 29 population-based congenital anomaly registries in 17 different countries. We calculated prevalence estimates, prenatal detection rate, survival up to 1 week, and proportions of associated anomalies. The effect of maternal age was tested using a Poisson regression model., Results: Out of 11 669 155 surveyed births, a total of 1294 cases of PRS were identified. The estimate of the overall prevalence was 12.0 per 100 000 births (95% CI 9.9, 14.5). There was a total of 882 (68.2%) isolated cases, and the prevalence was 7.8 per 100 000 births (95% CI 6.7, 9.2). A total of 250 cases (19.3%) were associated with other structural congenital anomalies, 77 cases (6.0%) were associated with chromosomal anomalies and 77 (6.0%) with genetic syndromes. The prenatal detection rate in isolated cases was 12.0% (95% CI 9.8, 14.5) and increased to 16.0% (95% CI 12.7, 19.7) in the sub-period 2008-2017. The prevalence rate ratio of non-chromosomal cases with maternal age ≥35 was higher than in cases with maternal age <25 for total (PRR 1.26, 95% CI 1.05, 1.51) and isolated cases (PRR 1.33, 95% CI 1.00, 1.64). Survival of chromosomal cases (94.2%) and multiple anomaly cases (95.3%) were lower than survival of isolated cases (99.4%)., Conclusions: This epidemiological study using a large series of cases of PRS provides insights into the epidemiological profile of PRS in Europe. We observed an association with higher maternal age, but further investigations are needed to test potential risk factors for PRS., (© 2021 John Wiley & Sons Ltd.)

Objective: Thirty years ago it was demonstrated that folic acid taken before pregnancy and in early pregnancy reduced the risk of a neural tube defect (NTD). Despite Public Health Initiatives across Europe recommending that women take 0.4 mg folic acid before becoming pregnant and during the first trimester, the prevalence of NTD pregnancies has not materially decreased in the EU since 1998, in contrast to the dramatic fall observed in the USA. This study aimed to estimate the number of NTD pregnancies that would have been prevented if flour had been fortified with folic acid in Europe from 1998 as it had been in the USA. Design and Setting: The number of NTD pregnancies from 1998 to 2017 that would have been prevented if folic acid fortification had been implemented in the 28 countries who were members of the European Union in 2019 was predicted was predicted using data on NTD prevalence from 35 EUROCAT congenital anomaly registries and literature searches for population serum folate levels and folic acid supplementation. Results: From 1998 to 2017 an estimated 95,213 NTD pregnancies occurred amongst 104 million births in the 28 countries in the EU, a prevalence of 0.92 per 1,000 births. The median serum folate level in Europe over this time period was estimated to be 14.1 μg/L. There is a lack of information about women taking folic acid supplements before becoming pregnant and during the first trimester of pregnancy, with one meta-analysis indicating that around 25% of women did so. An estimated 14,600 NTD pregnancies may have been prevented if the European countries had implemented fortification at the level adopted by the USA in 1998 and 25% of women took folic acid supplements. An estimated 19,500 NTD pregnancies would have been prevented if no women took folic acid supplements. Conclusions: This study suggests that failure to implement mandatory folic acid fortification in the 28 European countries has caused, and continues to cause, neural tube defects to occur in almost 1,000 pregnancies every year., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Morris, Addor, Ballardini, Barisic, Barrachina-Bonet, Braz, Cavero-Carbonell, Den Hond, Garne, Gatt, Haeusler, Khoshnood, Lelong, Kinsner-Ovaskainen, Kiuru-Kuhlefelt, Klungsoyr, Latos-Bielenska, Limb, O'Mahony, Perthus, Pierini, Rankin, Rissmann, Rouget, Sayers, Sipek, Stevens, Tucker, Verellen-Dumoulin, de Walle, Wellesley, Wertelecki and Bermejo-Sanchez.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Rouget, Bihannic, Cordier, Multigner, Meyer-Monath, Mercier, Pladys and Garlantezec.)

Background: Maternal occupational exposure to organic solvents during pregnancy has been associated with decreased visual function in offspring. Glycol ethers (GEs) belong to oxygenated solvents and are widely used both in occupational and domestic contexts., Objectives: We aimed to assess associations between prenatal GEs exposure and contrast sensitivity in children., Methods: Six GE alkoxy carboxylic acidic metabolites (methoxyacetic acid [MAA], ethoxyacetic acid [EAA], ethoxyethoxyacetic acid [EEAA], butoxyacetic acid [BAA], phenoxyacetic acid [PhAA], and 2-methoxypropionic acid [2-MPA]) were measured in first morning void urine samples collected from 220 early-pregnancy women, in the mother-child PELAGIE cohort (France). Trained investigators administered the Functional Acuity Contrast Test (FACT) to the 6-year-old children, providing scores for 5 spatial frequencies (1.5-18 cycles per degree (cpd)). We standardized biomarker urinary concentrations on urine sampling conditions. Values below the LOD were imputed based on log-normal distribution, generating five datasets for multiple imputation. Linear regression models were adjusted for potential confounders., Results: GE metabolites were detected in 70-98% of maternal urine samples. Phenoxyacetic acid (PhAA) had the highest median concentration (0.33 mg/L), and 2-methoxypropionic acid (2-MPA) the lowest (0.01 mg/L). Children with higher prenatal PhAA concentrations had poorer FACT scores at various spatial frequencies (fourth vs. first quartile: β 18cpd  = -0.90 (95% confidence interval CI = -1.64, -0.16), β 12cpd  = -0.92 (95%CI = -1.55, -0.29) and β 1.5cpd  = -0.69 (95%CI = -1.19, -0.20)). The 2-MPA log-scale concentration was negatively associated with the FACT score at the 3-cpd stimulus., Discussion: PhAA is the metabolite of ethylene glycol monophenyl ether present in many cosmetics. 2-MPA is the metabolite of an isomer of propylene glycol methyl ether commonly present in household and industrial cleaning products. Although evidence of biological plausibility is lacking, the study suggests adverse impact of ubiquitous prenatal exposure to some GE on visual functioning among children., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

Chlordecone is an organochlorine pesticide that was extensively used to control the banana root borer population in the French West Indies until 1993. Its persistence in soil has led to widespread pollution of the environment, and human beings, including pregnant women, are still exposed to this chemical. High levels of exposure to chlordecone during gestation have been shown to cause congenital anomalies, including undescended testes in rodents. We assessed the associations between chlordecone concentrations in maternal and cord plasma and the risk of congenital anomalies in the Timoun Mother-Child Cohort Study (2004-2007) that included 1068 pregnant women in Guadeloupe. Odds ratios were estimated using unconditional logistic regression analysis, controlling for confounding factors. The median plasma concentrations in maternal and cord plasma were 0.39 μg/L and 0.20 μg/L, respectively. Thirty-six children were diagnosed with malformations according to the European Registration of Congenital Anomalies guidelines and 25 with undescended testes. There was no association between maternal or cord plasma concentration of chlordecone and the risk of overall malformations nor undescended testes. These results suggest that prenatal exposure to the currently observed environmental levels of chlordecone in French West Indies does not increase the risk of birth defects.

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.

Glycol ethers are an oxygenated solvent family widely present in consumer products. Some of them are recognized reproductive, developmental or hematological toxicants. Although several glycol ether biomonitoring studies have been performed on adults from working or general populations, no studies have hitherto been carried out on children. The aim of our study was to explore the detection of glycol ether metabolites in the urinary samples of 6-year-old children, and if any were found, to describe them. The PELAGIE mother-child cohort included 3421 pregnant women from the general population of Brittany, France, between 2002 and 2006. Our biomonitoring study included a random sample of 110 children from the PELAGIE cohort who had participated in a neurodevelopment evaluation at the age of six. First morning voids were collected from all of the children. Eight urinary glycol ether metabolites were measured using gas chromatography with mass spectrometry. The limit of detection was 0.003 mg/L for all metabolites. Glycol ether metabolites were detected at rates varying from 33.5% of samples for propoxyacetic acid to 100% of samples for phenoxyacetic acid and methoxyacetic acid. The highest median concentration observed was for phenoxyacetic acid (0.141 mg/l). Our study reported the ubiquitous presence of glycol ether metabolites in children's urinary samples. These results call for larger biomonitoring surveys of the general population and study of the potential sources and determinants of these exposures., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

Desert dust transported from the Sahara to the Caribbean generates peak exposures to particulate matter ≤ 10 μm (PM 10 ). We investigated the impact of dust episodes on severe small for gestational-age births in Guadeloupe. The study sample consisted of 911 pregnant women enrolled in the Timoun mother-child cohort. Desert dust exposure was assessed through the mean daily PM 10 concentrations averaged over the entire pregnancy. Numerous sociodemographic and medical risk factors were considered as covariates and introduced into multinomial logistic regression models. Odds ratios (ORs) were calculated per SD change (3.08 μg/m 3 ). Among various outcomes, symmetrically growth-retarded births showed the highest OR (3.28, 95% CI: 1.08-10.02). Saharan dust seems to influence weight but not length or head circumference at birth. Given the high OR observed in this study, it is conceivable that Saharan dust plays a role through severe placental insufficiency early in pregnancy.

Background: The VACTERL association (VACTERL) is the nonrandom occurrence of at least three of these congenital anomalies: vertebral, anal, cardiac, tracheoesophageal, renal, and limb anomalies. Despite suggestions for involvement of several genes and nongenetic risk factors from small studies, the etiology of VACTERL remains largely unknown., Objective: To identify maternal risk factors for VACTERL in offspring in a large European study., Methods: A case-control study was performed using data from 28 EUROCAT registries over the period 1997-2015 with case and control ascertainment through hospital records, birth and death certificates, questionnaires, and/or postmortem examinations. Cases were diagnosed with VACTERL, while controls had a genetic syndrome and/or chromosomal abnormality. Data collected included type of birth defect and maternal characteristics, such as age, use of assisted reproductive techniques (ART), and chronic illnesses. Multivariable logistic regression analyses were performed to estimate confounder adjusted odds ratios (aOR) with 95% confidence intervals (95% CI)., Results: The study population consisted of 329 VACTERL cases and 49,724 controls with recognized syndromes or chromosomal abnormality. For couples who conceived through ART, we found an increased risk of VACTERL (aOR 2.3 [95% CI 1.3, 3.9]) in offspring. Pregestational diabetes (aOR 3.1 [95% CI 1.1, 8.6]) and chronic lower obstructive pulmonary diseases (aOR 3.9 [95% CI 2.2, 6.7]) also increased the risk of having a child with VACTERL. Twin pregnancies were not associated with VACTERL (aOR 0.6 [95% CI 0.3, 1.4])., Conclusion: We identified several maternal risk factors for VACTERL in offspring befitting a multifactorial etiology., (© 2020 The Authors. Birth Defects Research published by Wiley Periodicals, Inc.)

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 ± 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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Exposure to glycol ethers (GEs) is suspected of impairing neurodevelopment in children, but the specific impact on their inhibitory capacity, a central deficit of ADHD, has never been studied. We aimed to assess the impact of prenatal exposure to GEs on the response inhibition of children aged six years., Methods: In total, 169 mother-child pairs from the French cohort PELAGIE (2002-2006) were studied. Maternal urinary concentrations of six GE metabolites (alkoxycarboxylic acids) were measured during pregnancy. Multiple imputation by quantile regression was used to handle non-detected values and the data were then classified into quartiles. Inhibition of children was evaluated by the Rhythmic Continuous Performance Test 90 (R-CPT90). The inhibition score (percentage of correct responses to non-target stimuli) was corrected for compliance with the instructions (percentage of correct responses to target stimuli). The analysis used a multiple linear regression model, adjusting for confounding factors for each metabolite., Results: Median concentrations of metabolites ranged from 0.02 mg/L (Ethoxyacetic acid, EAA) to 0.39 mg/L (Phenoxyacetic acid, PhAA). The median corrected inhibition score was 37.9% [first quartile: 29.8 - third quartile: 47.9]. We found a negative and statistically significant association between the inhibition score and prenatal urinary EAA concentration (p-trend = 0.03), with a significant β coefficient for the third quartile (β = -0.064; 95% confidence interval: -0.121, -0.007). There were no statistically significant associations for the other five metabolites., Conclusion: These results are consistent with the hypothesis of possible impact of prenatal environmental exposure on inhibitory capacity among children. Data about the GEs metabolized to EAA (history of exposure sources and toxicokinetics) should be gathered to further interpret these results and guide precautionary measures., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: The VACTERL (Vertebral anomalies, Anal atresia, Cardiac malformations, Tracheo-Esophageal fistula, Renal anomalies, Limb abnormalities) association is the non-random occurrence of at least three of these congenital anomalies: vertebral, anal, cardiac, tracheo-esophageal, renal, and limb anomalies. Diagnosing VACTERL patients is difficult, as many disorders have multiple features in common with VACTERL. The aims of this study were to clearly outline component features, describe the phenotypic spectrum among the largest group of VACTERL patients thus far reported, and to identify phenotypically similar subtypes., Methods: A case-only study was performed assessing data on 501 cases recorded with VACTERL in the JRC-EUROCAT (Joint Research Centre-European Surveillance of Congenital Anomalies) central database (birth years: 1980-2015). We differentiated between major and minor VACTERL features and anomalies outside the VACTERL spectrum to create a clear definition of VACTERL., Results: In total, 397 cases (79%) fulfilled our VACTERL diagnostic criteria. The most commonly observed major VACTERL features were anorectal malformations and esophageal atresia/tracheo-esophageal fistula (both occurring in 62% of VACTERL cases), followed by cardiac (57%), renal (51%), vertebral (33%), and limb anomalies (25%), in every possible combination. Three VACTERL subtypes were defined: STRICT-VACTERL, VACTERL-LIKE, and VACTERL-PLUS, based on severity and presence of additional congenital anomalies., Conclusion: The clearly defined VACTERL component features and the VACTERL subtypes introduced will improve both clinical practice and etiologic research.

Objectives: To describe the epidemiology and geographical differences in prevalence of congenital cerebral anomalies in Europe., Design and Setting: Congenital cerebral anomalies (International Classification of Diseases, 10th Revision code Q04) recorded in 29 population-based EUROCAT registries conducting surveillance of 1.7 million births per annum (29% of all European births)., Participants: All birth outcomes (live births, fetal deaths from 20 weeks gestation and terminations of pregnancy after prenatal diagnosis of a fetal anomaly (TOPFA)) from 2005 to 2014., Main Outcome Measures: Prevalence, proportion of associated non-cerebral anomalies, prenatal detection rate., Results: 4927 cases with congenital cerebral anomalies were identified; a prevalence (adjusted for under-reporting) of 9.8 (95% CI: 8.5 to 11.2) per 10 000 births. There was a sixfold difference in prevalence across the registries. Registries with higher proportions of prenatal diagnoses had higher prevalence. Overall, 55% of all cases were liveborn, 3% were fetal deaths and 41% resulted in TOPFA. Forty-eight per cent of all cases were an isolated cerebral anomaly, 25% had associated non-cerebral anomalies and 27% were chromosomal or part of a syndrome (genetic or teratogenic). The prevalence excluding genetic or chromosomal conditions increased by 2.4% per annum (95% CI: 1.3% to 3.5%), with the increases occurring only for congenital malformations of the corpus callosum (3.0% per annum) and 'other reduction deformities of the brain' (2.8% per annum)., Conclusions: Only half of the cases were isolated cerebral anomalies. Improved prenatal and postnatal diagnosis may account for the increase in prevalence of congenital cerebral anomalies from 2005 to 2014. However, major differences in prevalence remain between regions., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (© 2019 Wiley Periodicals, Inc.)