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Can events that occurred during pregnancy have caused my child’s autism?

November 2, 2010 20 comments

“Got Questions?” is a new weekly feature on our blog to address the desire for scientific understanding in our community.  We received over 3000 responses when we asked what science questions were on your mind. We answered a few here and the Autism Speaks Science staff will address the other themes we received in this weekly post.

Many families have emailed us and asked what exposures in pregnancy result in an increased risk for an Autism Spectrum Disorder diagnosis. The answer is not simple.  No single environmental factor or single gene is responsible for causing ASD. Instead research suggests that a combination of multiple genetic and environmental factors lead to the multiple symptoms of autism.

By studying large populations, research on environmental exposures in autism has identified some exposures that increase the risk of autism in specific populations.   Interestingly, these exposures have been linked to poor neurological outcome in general, and may lead to a wider range of neurodevelopmental conditions that includes autism.  Three exposures have been shown to increase the risk for ASD in at least two published studies:

Pesticides: Two separate studies examining families living in California reported an increased risk of autism spectrum disorders following prenatal pesticide exposure.  In the first study,  Dr. Brenda Eskinazi at the University of California Berkley studied a group of Mexican-American children with known organophosphate exposures. She found that children who had increased levels of the break-down products of these pesticides were more likely to have impaired cognitive development at young ages as well an increased risk for pervasive developmental disorder (as reported by parents). In another study, Dr. Eric Roberts and his colleagues at the California Department of Public Health used informational databases to study possible connections between an ASD diagnosis and organochlorine pesticide exposure during different points of gestation. They found that those living closest to the area of pesticide application early in the 2nd trimester of pregnancy were at the highest risk for developing ASD.

Following up on these epidemiological studies, Autism Speaks is funding researchers who are utilizing animal models to determine possible genetic susceptibilities and neurobiological mechanisms.  For example, animals that have been bred to display an altered expression of the REELIN protein show particular sensitivity to organophosphate pesticides. Prenatal exposure to organophosphates disturbs the migration of developing neurons especially in animals that have lower levels of REELIN. Altered effects on the developing neurons can lead to atypically-connected adult brain circuits—a finding commonly observed in ASD.

Valproic Acid: Valproic Acid, or Valproate, is an anti-epileptic drug which targets the GABA receptor in the brain and has been effectively used to treat seizures.   When taken by the mother during the first few weeks of pregnancy, it can cause limb malformations, developmental delays, and musculoskeletal abnormalities, called “fetal valproate syndrome”.  The first report of autism in an individual with fetal valproate syndrome was published in 1994, with follow up in an animal model soon after.  Since then, four epidemiological studies have been published which show an increased rate of autism compared to the general population in individuals exposed prenatally with valproic acid.  In an animal model, valproic acid results in some of the same neuropathological and behavioral abnormalities seen in autism:  reduction in cerebellar Purkinje cells and an increase in social impairment.

Because this is a drug used to treat a life-threatening illness, women with epilepsy should consult their obstetrician before stopping this or any prescribed medication.  Interestingly, the use of other anti-epileptic drugs during pregnancy has not revealed any elevated risk for ASD. The differences in the detailed mechanism of action between valproate and other anti-epileptic drugs may inform our understanding of the causes of autism. Autism Speaks is supporting two investigations into the biological mechanisms that lead to brain and behavioral changes after prenatal exposure to valproate

Challenges to the immune system: Multiple lines of converging evidence suggest that the immune system plays a significant role in ASD.  This evidence includes studies that analyze the immune system profiles of mothers of children with autism, as well as the immune system of individuals with autism themselves.  Family history of autoimmunity or immune dysfunction and a history of bacterial infection in mothers have been associated with an increased risk of ASD.  More targeted studies on how immune system activation during pregnancy affects outcome in animal models are being funded by Autism Speaks to determine how the nature, origin, and timing of immune system activation can influence the developing brain.

Numerous other exposures have been studied and have shown an elevated risk but are still in the early stages of analysis.  These include, but are not limited to: phthalates (substances added to plastics), in-vitro fertilization technologies, terbutaline (a treatment used to delay premature labor), and extreme maternal stress.

In addition to environmental exposures, factors such as parental age and season of birth are likely to play a role in how the body handles exposure during the reproductive years.  For more information on what studies Autism Speaks is funding on environmental risk factors for autism, please click here.

While individual studies are needed to identify potential exposures of interest, participation and support in these studies is essential to allow researchers to study these questions.  Three major Autism Speaks-supported studies currently addressing these questions are the CHARGE study, the EARLI study, and the Infant Brain Imaging Study.  Another important study examining environmental risk factors related to health, including autism is the National Children’s Study.  Each study employs a unique design to recruit families and identify individuals with ASD for better identification and evaluation of exposures of interest, and all of them have great potential to shed light on prenatal risk factors for ASD.


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