Dataset Information

Prenatal Exposure to Endocrine-disrupting Chemicals in Relation to Autism Spectrum Disorder and Intellectual Disability.

ABSTRACT: BACKGROUND:Exposure to endocrine disruptors is unavoidable. Many such compounds are suspected to impact neurologic development of children, but most studies conducted have considered effects of individual chemicals in isolation. Because exposures co-occur, it is important to consider their health impacts in a single regression framework. METHODS:We applied Bayesian statistical tools (including shared mean and mixture priors for 25 unique chemicals) to study independent associations of endocrine disruptor biomarkers with autism spectrum disorder (ASD) (n = 491) and intellectual disability (n = 155), compared with 373 general population controls, in the Early Markers for Autism study. We measured biomarkers in maternal serum collected and stored from midpregnancy and considered them individually or as a class (i.e., summed polychlorinated biphenyls). We adjusted all models for original matching factors (child sex and month and year of birth), maternal age, maternal race/ethnicity, parity, and maternal education at the time samples were collected. We estimated the change in the odds of ASD or intellectual disability per 1 SD increase in the z-score of measured biomarker concentration for each chemical. RESULTS:Odds of ASD and intellectual disability did not change with increasing concentration for any specific endocrine disruptor. The effect estimates for each chemical were centered on or near an odds ratio of 1.00 in both models where we applied a shared mean or a mixture prior. CONCLUSION:Our mixtures analyses do not suggest an independent relationship with ASD or intellectual disability with any of the 25 chemicals examined together in this mixtures analysis.

SUBMITTER: Hamra GB

PROVIDER: S-EPMC6456403 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Prenatal Exposure to Endocrine-disrupting Chemicals in Relation to Autism Spectrum Disorder and Intellectual Disability.

Hamra Ghassan B GB Lyall Kristen K Windham Gayle C GC Calafat Antonia M AM Sjödin Andreas A Volk Heather H Croen Lisa A LA

Epidemiology (Cambridge, Mass.) 20190501 3

<h4>Background</h4>Exposure to endocrine disruptors is unavoidable. Many such compounds are suspected to impact neurologic development of children, but most studies conducted have considered effects of individual chemicals in isolation. Because exposures co-occur, it is important to consider their health impacts in a single regression framework.<h4>Methods</h4>We applied Bayesian statistical tools (including shared mean and mixture priors for 25 unique chemicals) to study independent association ...[more]

PMID: 30789431

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Project description:Autism spectrum disorder (ASD) is highly heritable, yet how its familial risk and heritability may vary by cognitive ability is not well understood. In this population-based cohort study, we examined the familial risk and heritability of ASD with and without co-occurring intellectual disability (ID). We estimated odds ratios and heritability of ASD with ID (ASD+ID) and ASD without ID (ASD-ID) using register-based diagnosis data of 567,436 index persons born in 1984-2009 in Stockholm County, Sweden, and their parents, siblings, cousins, aunts, and uncles. The familial risk profile exhibited differences between ASD-ID and ASD+ID, most notably for index persons with affected parents. For example, for an index person who had at least one parent with ASD, the child's odds of ASD-ID and ASD+ID (95% confidence interval (CI)) increased by 16.2 (14.2-18.6) and 7.4 (5.5-10.0) folds, respectively. The more closely related a family member with ASD was, the greater the observed risk was of ASD in the index person, especially for ASD-ID. The broad-sense heritability (95% CI) for ASD - ID and ASD+ID were 64.6% (46.0-100.0%) and 33.4% (14.4-58.4%), respectively. Familial risk and heritability of ASD may vary by intellectual ability, which implies that risk factors between these ASD phenotypes may differ. Our findings from the heritability analysis and familial risk analysis suggest that ASD-ID may have a greater genetic basis than ASD+ID, although this should be verified in future studies. LAY SUMMARY: Autism spectrum disorder (ASD) is highly heritable, yet how its familial risk and heritability may vary by cognitive ability is not well-understood. In a population-based cohort study on families of 567,436 index persons using Swedish registers data, we found that the familial risk profile differed between ASD with and without intellectual disability. Our findings from the heritability analysis and familial risk analysis suggest that ASD-ID may have a greater genetic basis than ASD+ID, although this should be verified in future studies.

Project description:Exposures to endocrine-disrupting chemicals (EDCs) affect the development of hormone-sensitive neural circuits, the proper organization of which are necessary for the manifestation of appropriate adult social and sexual behaviors. We examined whether prenatal exposure to polychlorinated biphenyls (PCBs), a family of ubiquitous industrial contaminants detectable in virtually all humans and wildlife, caused changes in sexually-dimorphic social interactions and communications, and profiled the underlying neuromolecular phenotype. Rats were treated with a PCB commercial mixture, Aroclor 1221 (A1221), estradiol benzoate (EB) as a positive control for estrogenic effects of A1221, or the vehicle (4% DMSO), on embryonic day (E) 16 and 18. In adult F1 offspring, we first conducted tests of ultrasonic vocalization (USV) calls in a sociosexual context as a measure of motivated communications. Numbers of certain USV call types were significantly increased by prenatal treatment with A1221 in males, and decreased by EB in females. In a test of sociosexual preference for a hormone-vs. a non-hormone-primed opposite sex conspecific, male (but not female) nose-touching with opposite-sex rats was significantly diminished by EDCs. Gene expression profiling was conducted in two brain regions that are part of the social decision-making network in the brain: the medial preoptic nucleus (MPN) and the ventromedial nucleus (VMN). In both regions, many more genes were affected by A1221 or EB in females than males. In female MPN, A1221 changed expression of steroid hormone receptor and neuropeptide genes (e.g., Ar, Esr1, Esr2, and Kiss1). In male MPN, only Per2 was affected by A1221. The VMN had a number of genes affected by EB compared to vehicle (females: Kiss1, Kiss1r, Pgr; males: Crh) but not A1221. These differences between EB and A1221 indicate that the mechanism of action of A1221 goes beyond estrogenic pathways. These data show sex-specific effects of prenatal PCBs on adult behaviors and the neuromolecular phenotype.

Dataset Information

Prenatal Exposure to Endocrine-disrupting Chemicals in Relation to Autism Spectrum Disorder and Intellectual Disability.

Publications

Prenatal Exposure to Endocrine-disrupting Chemicals in Relation to Autism Spectrum Disorder and Intellectual Disability.

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