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Influence of Low-Level Prenatal Exposure to PCDD/Fs and PCBs on Empathizing, Systemizing and Autistic Traits: Results from the Duisburg Birth Cohort Study.

ABSTRACT: Polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and polychlorinated biphenyls (PCBs) are assumed to act as endocrine disruptor chemicals. Prenatal exposure to these pollutants might influence fetal steroid hormone levels, which are thought to be related to sex-typical development and autistic traits.We examined associations of prenatal levels of PCDD/Fs and PCBs with autism traits and sex-typical behaviour in childhood.We measured levels of PCDD/Fs and PCBs in maternal blood samples during pregnancy using gas chromatography/high-resolution mass spectrometry. Sex-typical behaviour was assessed at 9 years of age (n = 96) and autistic traits at 10 years of age using the Social Responsiveness Scale (SRS; n = 100). Multiple regression analyses were conducted to estimate the associations between prenatal exposure and outcome variables.Blood concentrations (WHO2005-TEq) of ƩPCDD/Fs ranged from 2.93-46.45 pg/g lipid base (median = 12.91 pg/g lipid base) and concentrations of ƩPCBs were in the range of 1.24-25.47 pg/g lipid base (median = 6.85 pg/g lipid base) which is within the range of German background exposure. We found significant negative associations between PCDD/F levels in maternal blood and SRS scores in the whole group (β = -6.66, p < .05), in girls (β = -10.98, p < .05) and, in one SRS subscale, in boys (β = -6.86, p < .05). For PCB levels, associations with one SRS subscale were significant for the whole study group as were associations with two subscales in girls. We did not find significant associations between PCDD/F or PCB levels and sex-typical behaviour for either sex.In an earlier part of this study, prenatal exposure to PCDD/Fs and PCBs was found to be associated with lower testosterone levels, therefore, our findings are consistent with the idea that autism spectrum conditions are related to fetal androgen levels. Several possible mechanisms, through which PCDD/Fs and PCBs might influence autistic behaviour, are discussed.

SUBMITTER: Nowack N

PROVIDER: S-EPMC4466566 | biostudies-other | 2015

REPOSITORIES: biostudies-other

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Project description:OBJECTIVES: Exposure to high concentrations of persistent organochlorines may cause fetal toxicity, but the evidence at low exposure levels is limited. Large studies with substantial exposure contrasts and appropriate exposure assessment are warranted. Within the framework of the EU (European Union) ENRIECO (ENvironmental Health RIsks in European Birth Cohorts) and EU OBELIX (OBesogenic Endocrine disrupting chemicals: LInking prenatal eXposure to the development of obesity later in life) projects, we examined the hypothesis that the combination of polychlorinated biphenyls (PCBs) and dichlorodiphenyldichloroethylene (DDE) adversely affects birth weight. METHODS: We used maternal and cord blood and breast milk samples of 7,990 women enrolled in 15 study populations from 12 European birth cohorts from 1990 through 2008. Using identical variable definitions, we performed for each cohort linear regression of birth weight on estimates of cord serum concentration of PCB-153 and p,p´-DDE adjusted for gestational age and a priori selected covariates. We obtained summary estimates by meta-analysis and performed analyses of interactions. RESULTS: The median concentration of cord serum PCB-153 was 140 ng/L (range of cohort medians 20-484 ng/L) and that of p,p´-DDE was 528 ng/L (range of cohort medians 50-1,208 ng/L). Birth weight decreased with increasing cord serum concentration of PCB-153 after adjustment for potential confounders in 12 of 15 study populations. The meta-analysis including all cohorts indicated a birth weight decline of 150 g [95% confidence interval (CI): -250, -50 g] per 1-µg/L increase in PCB-153, an exposure contrast that is close to the range of exposures across the cohorts. A 1-µg/L increase in p,p´-DDE was associated with a 7-g decrease in birth weight (95% CI: -18, 4 g). CONCLUSIONS: The findings suggest that low-level exposure to PCB (or correlated exposures) impairs fetal growth, but that exposure to p,p´-DDE does not. The study adds to mounting evidence that low-level exposure to PCBs is inversely associated with fetal growth.

Project description:Organophosphorous (OP) pesticides are associated with reduced fetal growth in animals, but human studies are inconsistent.We pooled data from four cohorts to examine associations of prenatal OP exposure with birth weight (n = 1,169), length (n = 1,152), and head circumference (n = 1,143).Data were from the CHAMACOS, HOME, Columbia, and Mount Sinai birth cohorts. Concentrations of three diethyl phosphate (?DEP) and three dimethyl phosphate (?DMP) metabolites of OP pesticides [summed to six dialkyl phosphates (?DAPs)] were measured in maternal urine. Linear regression and mixed-effects models were used to examine associations with birth outcomes.We found no significant associations of ?DEP, ?DMP, or ?DAPs with birth weight, length, or head circumference overall. However, among non-Hispanic black women, increasing urinary ?DAP and ?DMP concentrations were associated with decreased birth length (? = -0.4 cm; 95% CI: -0.9, 0.0 and ? = -0.4 cm; 95% CI: -0.8, 0.0, respectively, for each 10-fold increase in metabolite concentration). Among infants with the PON1192RR genotype, ?DAP and ?DMP were negatively associated with length (? = -0.4 cm; 95% CI: -0.9, 0.0 and ? = -0.5 cm; 95% CI: -0.9, -0.1).This study confirms previously reported associations of prenatal OP exposure among black women with decreased infant size at birth, but finds no evidence of smaller birth weight, length, or head circumference among whites or Hispanics. Contrary to our hypothesis, we found stronger inverse associations of DAPs and birth outcome in infants with the less susceptible PON1192RR genotype. The large pooled data set facilitated exploration of interactions by race/ethnicity and PON1 genotype, but was limited by differences in study populations.Harley KG, Engel SM, Vedar MG, Eskenazi B, Whyatt RM, Lanphear BP, Bradman A, Rauh VA, Yolton K, Hornung RW, Wetmur JG, Chen J, Holland NT, Barr DB, Perera FP, Wolff MS. 2016. Prenatal exposure to organophosphorous pesticides and fetal growth: pooled results from four longitudinal birth cohort studies. Environ Health Perspect 124:1084-1092; http://dx.doi.org/10.1289/ehp.1409362.

Project description:BackgroundA high prevalence of autism spectrum disorder is reported in children born extremely preterm (EP), but an even larger proportion of survivors are affected by subclinical difficulties than meet diagnostic criteria. The aims of this study were to investigate autistic traits associated with the broader autism phenotype in a cohort of young adults born EP, and explore how these traits relate to emotion recognition, empathy and autism symptom presentation in childhood. The prevalence of autism diagnoses was also investigated.MethodsOne hundred and twenty-nine young adults born before 26 weeks of gestation and 65 term-born controls participated in the 19-year follow-up phase of the EPICure studies. In addition to a clinical interview, participants completed the Broader Autism Phenotype Questionnaire (BAPQ), the Empathy Quotient questionnaire, and the Frankfurt Test and Training of Facial Affect Recognition. The Social Communication Questionnaire (SCQ) was completed by the participants' parents at age 11 years.ResultsEP born young adults scored significantly higher on the BAPQ in comparison with their term-born peers, indicating greater autistic traits. Among EP participants, BAPQ scores were correlated with SCQ scores in childhood (r = 0.484, p < 0.001). EP young adults had significantly lower scores in emotion recognition and empathy in comparison with controls; however, this effect was mediated by IQ. At 19 years, a diagnosis of autism was reported by 10% of EP participants versus 1.6% of controls, whereas 31% of EP participants scored above the cut-off for the broader autism phenotype in comparison with 8.5% of term-born controls.LimitationsThe high attrition of EP participants from lower socio-economic backgrounds and with lower cognitive functioning may have led to an underrepresentation of those presenting with difficulties associated with autism.ConclusionsA larger proportion of EP survivors are affected by difficulties associated with autism than have confirmed diagnoses, with a moderate correlation between autism symptom scores in childhood and autistic traits in young adulthood. EP young adults had significantly higher autism symptom scores and a larger proportion had a diagnosis of autism than controls. Screening for autistic traits at set points throughout childhood will help identify those EP individuals at risk of social difficulties who may benefit from intervention.

Project description:BackgroundPolychlorinated biphenyls (PCBs), methylmercury (MeHg), and lead (Pb) are environmental contaminants known for their adverse effects on cognitive development.ObjectivesIn this study we examined the effects of prenatal exposure to PCBs, MeHg, and Pb on cognitive development in a sample of Inuit infants from Arctic Québec.MethodsMothers were recruited at local prenatal clinics. PCBs, mercury (Hg), Pb, and two seafood nutrients-docosahexaenoic acid (DHA) and selenium (Se)-were measured in umbilical cord blood. Infants (n = 94) were assessed at 6.5 and 11 months of age on the Fagan Test of Infant Intelligence (FTII), A-not-B test, and Bayley Scales of Infant Development-2nd Edition (BSID-II).ResultsMultiple regression analyses revealed that higher prenatal PCB exposure was associated with decreased FTII novelty preference, indicating impaired visual recognition memory. Prenatal Hg was associated with poorer performance on A-not-B, which depends on working memory and is believed to be a precursor of executive function. Prenatal Pb was related to longer FTII fixation durations, indicating slower speed of information processing.ConclusionsPCBs, MeHg, and Pb each showed specific and distinct patterns of adverse associations with the outcomes measured during infancy. By contrast, none of these exposures was associated with performance on the BSID-II, a global developmental measure. The more focused, narrow band measures of cognitive function that appeared to be sensitive to these exposures also provide early indications of long-term impairment in specific domains that would otherwise not likely be evident until school age.CitationBoucher O, Muckle G, Jacobson JL, Carter RC, Kaplan-Estrin M, Ayotte P, Dewailly É, Jacobson SW. 2014. Domain-specific effects of prenatal exposure to PCBs, mercury, and lead on infant cognition: results from the Environmental Contaminants and Child Development Study in Nunavik. Environ Health Perspect 122:310-316;?http://dx.doi.org/10.1289/ehp.1206323.

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Influence of Low-Level Prenatal Exposure to PCDD/Fs and PCBs on Empathizing, Systemizing and Autistic Traits: Results from the Duisburg Birth Cohort Study.

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