Maternal exposure to workplace solvents may increase the risk for ASD in children

The CHARGE study : an assessment of parental occupational exposures and autism spectrum disorder

Children whose mothers are exposed to solvents at work are at higher risk of autism, shows new research.

The study found that women who are exposed to workplace solvents are 1.5 times more likely to have a child on the autistic spectrum, newnationnews reports. Image credit @ATEN_Int.

2019 Study Abstract

Objectives
The aim of this study is to determine if parental occupational exposure to 16 agents is associated with autism spectrum disorder (ASD).

Methods
Demographic, health and parental occupational data were collected as part of the CHildhood Autism Risks from Genetics and Environment (CHARGE) study. The workplace exposure assessment was conducted by two experienced industrial hygienists for the parents of 537 children with ASD and 414 typically developing (TD) children. For each job, frequency and intensity of 16 agents were assessed and both binary and semi-quantitative cumulative exposure variables were derived. Logistic regression models were used to calculate adjusted odds ratios (OR) and 95% confidence intervals (CI) to assess associations between parental occupational exposures 3 months pre-pregnancy until birth.

Results
The OR of ASD in the children of mothers exposed to any solvents was 1.5 times higher than the mothers of TD children (95% CI=1.01–2.23). Cumulative exposure indicated that the OR associated with a moderate level of solvent exposure in mothers was 1.85 (95% CI=1.09, 3.15) for children with ASD compared with TD children. No other exposures were associated with ASD in mothers, fathers or the parents combined.

Conclusion
Maternal occupational exposure to solvents may increase the risk for ASD. These results are consistent with a growing body of evidence indicating that environmental and occupational exposures may be associated with ASD. Future research should consider specific types of solvents, larger samples and/or different study designs to evaluate other exposures for potential associations with ASD.

Impact of male factor infertility on offspring health and development

Long-term health and developmental outcomes in children conceived with intracytoplasmic sperm injection

2019 Study Abstract

Monitoring the safety of intracytoplasmic sperm injection (ICSI) has been impeded by uncertainties regarding the extent to which offspring health is influenced by paternal characteristics linked to male infertility or the processes that ICSI treatment entails.

Few studies examining long-term health and developmental outcomes in children conceived with ICSI have considered the influence of paternal infertility adequately.

In the available literature, large population-based studies suggest underlying male factors, and the severity of male factor infertility, increase the risk of mental retardation and autism in offspring, as does the ICSI procedure itself, but these findings have not been replicated consistently.

Robust evidence of the influence of male factors on other health outcomes is lacking, with many studies limited by sample size.

Nevertheless, emerging evidence suggests children conceived with ICSI have increased adiposity, particularly girls.

Further, young men conceived with ICSI may have impaired spermatogenesis; the mechanisms underlying this remain unclear, with inconclusive evidence of inheritance of Y chromosome microdeletions.

The current inconsistent and often sparse literature concerning the long-term health of children conceived with ICSI, and the specific influence of male infertility factors, underscore the need for concerted monitoring of children conceived with this technique across the lifespan.

With the rapid expansion of use of ICSI for non-male factors, sufficiently large studies that compare outcomes between groups conceived with this technique for male factors versus non-male factors will provide critical evidence to elucidate the intergenerational impact of male infertility.

Reference. Image credit fertilitysmarts.

May Processed Foods Hold Key to Rise in Autism ?

Propionic Acid Induces Gliosis and Neuro-inflammation through Modulation of PTEN/AKT Pathway in Autism Spectrum Disorder

With the number of children diagnosed with autism on the rise, the need to find what causes the disorder becomes more urgent every day.
UCF researchers are now a step closer to showing the link between the food pregnant women consume and the effects on a fetus’ developing brain.

2019 Study Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by glia over-proliferation, neuro-inflammation, perturbed neural circuitry, and gastrointestinal symptoms. The role of gut dys-biosis in ASD is intriguing and should be elucidated.

We investigated the effect of Propionic acid (PPA), a short-chain fatty acid (SCFA) and a product of dys-biotic ASD gut, on human neural stem cells (hNSCs) proliferation, differentiation and inflammation.

hNSCs proliferated to 66 neuropsheres when exposed to PPA versus 45 in control. The neurosphere diameter also increased at day 10 post PPA treatment to (Mean: 193.47 um ± SEM: 6.673 um) versus (154.16 um ± 9.95 um) in control, p < 0.001. Pre-treatment with β-HB, SCFA receptor inhibitor, hindered neurosphere expansion (p < 0.001). While hNSCs spontaneously differentiated to (48.38% ± 6.08%) neurons (Tubulin-IIIβ positive) and (46.63% ± 2.5%) glia (GFAP positive), PPA treatment drastically shifted differentiation to 80% GFAP cells (p < 0.05). Following 2 mM PPA exposure, TNF-α transcription increased 4.98 fold and the cytokine increased 3.29 fold compared to control (P < 0.001). Likewise, GPR41 (PPA receptor) and pro-survival p-Akt protein were elevated (p < 0.001). PTEN (Akt inhibitor) level decreased to (0.42 ug/ul ± 0.04 ug/ul) at 2 mM PPA compared to (0.83 ug/ul ± 0.09 ug/ul) in control (p < 0.001). PPA at 2 mM decreased neurite outgrowth to (80.70 um ± 5.5 um) compared to (194.93 um ± 19.7 um) in control.

Clearly, the data supports a significant role for PPA in modulating hNSC patterning leading to gliosis, disturbed neuro-circuitry, and inflammatory response as seen in ASD.

Chlorpyrifos : another pesticide that must be banned

The EU approval of the brain-damaging pesticide chlorpyrifos was based on one single biased study – commissioned by industry…

The Cross-border investigation on chlorpyrifos was initiated by Investigative Reporting Denmark and Danwatch, and made in collaboration with journalists from Knack in Belgium, Le Monde in France, Dagbladet in Norway, Newsweek in Poland, Ostro in Slovenia, El Confidential in Spain and The Midwest Center for Investigative Reporting in US. The investigation was supported by Journalismfund.eu.

Environmental Chemicals and Autism

A Scoping Review of the Human and Animal Research, 2019

The Endocrine Disruption Exchange newest scoping review finds that 152 environmental chemicals have been investigated in humans or animals for their association with autism. TEDX highlight the need for systematic review of lead, PCBs, and chlorpyrifos.

Abstract

Background
Estimates of autism prevalence have increased dramatically over the past two decades. Evidence suggests environmental factors may contribute to the etiology of the disorder.

Objectives
This scoping review aimed to identify and categorize primary research and reviews on the association between prenatal and early postnatal exposure to environmental chemicals and the development of autism in epidemiological studies and rodent models of autism.

Methods
PubMed was searched through 8 February 2018. Included studies assessed exposure to environmental chemicals prior to 2 months of age in humans or 14 d in rodents. Rodent studies were considered relevant if they included at least one measurement of reciprocal social communicative behavior or repetitive and stereotyped behavior. Study details are presented in interactive displays using Tableau Public.

Results
The search returned 21,603 unique studies, of which 54 epidemiological studies, 46 experimental rodent studies, and 50 reviews were deemed relevant, covering 152 chemical exposures. The most frequently studied exposures in humans were particulate matter (n=14), mercury (n=14), nonspecific air pollution (n=10), and lead (n=10). In rodent studies, the most frequently studied exposures were chlorpyrifos (n=9), mercury (n=6), and lead (n=4).

Discussion
Although research is growing rapidly, wide variability exists in study design and conduct, exposures investigated, and outcomes assessed. Conclusions focus on recommendations to guide development of best practices in epidemiology and toxicology, including greater harmonization across these fields of research to more quickly and efficiently identify chemicals of concern. In particular, we recommend chlorpyrifos, lead, and polychlorinated biphenyls (PCBs) be systematically reviewed in order to assess their relationship with the development of autism. There is a pressing need to move forward quickly and efficiently to understand environmental influences on autism in order to answer current regulatory questions and inform treatment and prevention efforts.

60 MiNueTs Toxic

UCSF Program on Reproductive Health and the Environment, 2017

Video published on 18 Apr 2019 by the UCSF Program on Reproductive Health and the Environment.

The University of California San Francisco (UCSF) Program on Reproductive Health and the Environment (PRHE)’s mission is to create a healthier environment for human reproduction and development through advancing scientific inquiry, clinical care and health policies that prevent exposures to harmful chemicals in our environment.

More Information

Why are ObGyns Talking Toxins ?

Let’s make environmental health part of health care

Doctors from 125 countries want policies to prevent exposure to toxic chemicals

Produced for PRHE by Susan Lamontagne, Public Interest Media Group, for the International Federation of Gynecology and Obstetrics (FIGO) XXI World Congress on September 30, 2015.

Why are Doctors Talking Toxins ?

And how to reduce exposure to toxic chemicals worldwide ?

It’s time to shift the burden of proof, from scientists, back to the chemical industry

Video published on 5 June 2019, by UCSF Program on Reproductive Health and the Environment.

Behavioral disorders in kids with autism linked to reduced brain connectivity

Reduced Amygdala–Prefrontal Functional Connectivity in Children With Autism Spectrum Disorder and Co-occurring Disruptive Behavior

Reduced connectivity between the amygdala and ventrolateral prefrontal cortex has been identified in children on the autism spectrum who exhibit disruptive behaviors, compared to those on the spectrum who do not. Findings suggest this distinct brain network could be independent of core autism symptoms.

More than a quarter of children with autism spectrum disorder are also diagnosed with disruptive behavior disorders. For the first time, Yale researchers have identified a possible biological cause: a key mechanism that regulates emotion functions differently in the brains of the children who exhibit disruptive behavior.

Neuroscience News reports, 21/04/2019.

2019 Study Abstract

Background

Disruptive behaviors are prevalent in children with autism spectrum disorder (ASD) and often cause substantial impairments. However, the underlying neural mechanisms of disruptive behaviors remain poorly understood in ASD. In children without ASD, disruptive behavior is associated with amygdala hyperactivity and reduced connectivity with the ventrolateral prefrontal cortex (vlPFC). This study examined amygdala reactivity and connectivity in children with ASD with and without co-occurring disruptive behavior disorders. We also investigated differential contributions of externalizing behaviors and callous-unemotional traits to variance in amygdala connectivity and reactivity.

Methods

This cross-sectional study involved behavioral assessments and neuroimaging in three groups of children 8 to 16 years of age: 18 children had ASD and disruptive behavior, 20 children had ASD without disruptive behavior, and 19 children were typically developing control participants matched for age, gender, and IQ. During functional magnetic resonance imaging, participants completed an emotion perception task of fearful versus calm faces. Task-specific changes in amygdala reactivity and connectivity were examined using whole-brain, psychophysiological interaction, and multiple regression analyses.

Results

Children with ASD and disruptive behavior showed reduced amygdala–vlPFC connectivity compared with children with ASD without disruptive behavior. Externalizing behaviors and callous-unemotional traits were associated with amygdala reactivity to fearful faces in children with ASD after controlling for suppressor effects.

Conclusions

Reduced amygdala–vlPFC connectivity during fear processing may differentiate children with ASD and disruptive behavior from children with ASD without disruptive behavior. The presence of callous-unemotional traits may have implications for identifying differential patterns of amygdala activity associated with increased risk of aggression in ASD. These findings suggest a neural mechanism of emotion dysregulation associated with disruptive behavior in children with ASD.

Screening for rare epigenetic variations in autism and schizophrenia

Additional evidence that rare epivariations likely contribute to the mutational spectra underlying neurodevelopmental disorders

2019 Study Abstract

While many studies have led to the identification of rare sequence variants linked with susceptibility to autism and schizophrenia, the contribution of rare epigenetic variations (epivariations) in these disorders remains largely unexplored.

Previously we presented evidence that epivariations occur relatively frequently in the human genome, and likely contribute to a subset of congenital and neurodevelopmental disorders through the disruption of dosage-sensitive genes.

Here we extend this approach, studying methylation profiles from 297 samples with autism and 767 cases with schizophrenia, identifying 84 and 268 rare epivariations in these two cohorts, respectively, that were absent from 4,860 population controls.

We observed multiple features associated with these epivariations that support their pathogenic relevance, including

  1. a significant enrichment for epivariations in schizophrenic individuals at genes previously linked with schizophrenia,
  2. increased brain expression of genes associated with epivariations found in autism cases compared with controls,
  3. in autism families, a significant excess of epivariations found specifically in affected versus unaffected sibs,
  4. Gene Ontology terms linked with epivariations found in autism, including “D1 dopamine receptor binding.”

Our study provides additional evidence that rare epivariations likely contribute to the mutational spectra underlying neurodevelopmental disorders. Image credit Brigham and Women’s Hospital.

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