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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, Introduction Per- and polyfluoroalkyl substances (PFAS) form a group of more than 9,000 synthetic chemicals that have been used worldwide for more than 70 y. Their surfactant properties have ensured [...]

BackgroundGlycol ethers (GE) are widely used organic solvents. Despite the potential neurotoxicity of several families of organic solvents, little is known about the impact of GE on the neurodevelopment of infants and children.ObjectivesWe investigated the relation between urinary concentrations of GE metabolites in pregnant women and neurocognitive abilities in their 6-year-old children in the PELAGIE mother-child cohort.MethodsFive GE metabolites were measured in first morning void urine samples of 204 French pregnant women in early pregnancy (< 19 weeks of gestation). Psychologists assessed the neurocognitive abilities of their 6-year-old children with the Wechsler Intelligence Scale for Children IV (WISC) and the Developmental Neuropsychological Assessment (NEPSY). We analyzed the results with linear (WISC) and Poisson regression models (NEPSY), adjusted for potential confounders, including child's stimulation at home.ResultsGE metabolites were detected in 90-100% of maternal urine samples. The WISC Verbal Comprehension score was significantly lower for children with the highest tertile of urinary phenoxyacetic acid (PhAA) [β (third vs. first tertile) = -6.53; 95% CI: -11.44, -1.62]. Similarly, the NEPSY Design Copying subtest score was lower in those with the highest tertile of urinary ethoxyacetic acid (EAA) [β (third vs. first tertile) = -0.11; 95% CI: -0.21, 0.00]. The other GE metabolites we studied were not significantly associated with WISC or NEPSY scores.ConclusionsPrenatal urine concentrations of two GE metabolites were associated with lower WISC Verbal Comprehension Index scores and NEPSY Design Copying subscale scores, respectively, at age 6 years. PhAA is the primary metabolite of 2-phenoxyethanol (EGPhE), which is commonly found in cosmetics, and precursors of EAA are frequently used in cleaning agents. Additional research is needed to confirm our findings and further explore potential effects of prenatal GE exposures on neurocognitive performance in children.

The PELAGIE mother-child cohort study, conducted in western France, aims to examine the impact of prenatal exposure to chemicals on pregnancy outcomes and child health. The study followed over 3,000 pregnant women and their newborns, collecting extensive data on chemical exposures and various health outcomes. The cohort is part of a European network and welcomes collaborations. The study found associations between prenatal exposure to solvents, pesticides, and persistent organic pollutants and adverse health effects in children. The data collected is available for further research. [Extracted from the article]

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 ncases = 13, ncontrols = 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. [ABSTRACT FROM AUTHOR]

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_tercile = −0.06 [−0.10,-0.03] and β3rd_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. [ABSTRACT FROM AUTHOR]