The Environment and ASD Risk: Putting It Together

Interviewer: Laurie Scudder, DNP, NP; Interviewees: Eliza M. Gordon-Lipkin, MD; Paul H. Lipkin, MD

Disclosures

July 27, 2017

'While there is no dispute that the prevalence of autism spectrum disorders (ASD) is on the rise, what is in question are the reasons for it. Genetics is recognized to play a major causal role in ASD. But over the past 5-10 years there has been a growing body of research examining the contribution of environmental factors. What are those environmental factors, and are there ways for families to mitigate these risks? Medscape spoke with Paul Lipkin, MD, the director of the Interactive Autism Network at the Kennedy Krieger Institute in Baltimore, Maryland, and Eliza Gordon-Lipkin, MD, neurodevelopmental and child neurology fellow, also at Kennedy Krieger, about this issue and the current state of research.

Medscape: One of the factors that has received a fair amount of attention is related to parental age. Is advanced maternal or paternal age a risk factor for an ASD in the child?

Eliza M. Gordon-Lipkin, MD

Dr Gordon-Lipkin: The evidence suggests that there is a connection between increased maternal and paternal age and the risk for autism. What we don't know at this point are the mechanisms. One area that is receiving attention is epigenetics—the concept that your genes are not necessarily fixed, and that there's an interaction between genes, environment, and other factors that can determine how the brain develops and how a child may be at risk for autism. It includes mechanisms like methylation, which can determine when a gene may be turned on or off during brain development.

Another etiology being investigated is the social determinants that affect a person's health. In other words, parents who have children at an older age may do so for multiple reasons, including both biological and social reasons. The reasons that they have a child later in life may also be tied to increased risk for ASD. For example, a woman who suffers from infertility is more likely to have a child at an older age and is also more likely to have a high-risk pregnancy which could put the fetus at risk. Alternatively, some hypothesize that subclinical ASD traits that affect personality may change social success and delay parenthood,[1] and these same traits may be passed down to children.

Maternal Factors: Meds, Diet, and Infections

Medscape: Maternal medications have also been implicated, although the data are pretty mixed. Is there any consensus that medication use during pregnancy is implicated in ASD etiology?

Paul H. Lipkin, MD

Dr Gordon-Lipkin: There is a lot of interest in antidepressant medication and the risk for autism, and I agree that there's mixed evidence. It's also important to consider, similar to the concept of advanced maternal age, that there are medical, psychiatric, and social factors that may influence a reason why a mother is on that medication in the first place. Those factors may be tied to the reasons for the increase in risk for autism. It is very important to consider the risks and the benefits of any given medication and the reasons why the mother may be on that medication in the first place. Controlling that factor is just as important as the possible risks of the medication itself.

Dr Lipkin: It has been very attractive in the medical-legal world to look for a direct cause and effect between medications and autism. There are cases circulating through the courts, for example, with paroxetine and some other medications. But direct cause-and-effect evidence is quite uncertain.

Implicit in the whole discussion around medications are these underlying genetic and social determinants that people bring into a pregnancy. Medication fits into that discussion as well.

Medscape What about the issue of maternal infections? Is there evidence that infections and/or fever are associated with ASD? If so, what kinds of infections, and is any particular gestational age of highest concern?

Dr Gordon-Lipkin: I think infections are important to consider. We can think of them in two categories: There are infections that have a direct effect on brain development, and then there are the infections that cause an inflammatory or fever response that indirectly affects brain development.

In the first category, we think about infections like cytomegalovirus (CMV) and, more recently, the Zika virus. CMV is prevalent in the environment. Many people have it and are not affected by it. However, when contracted during pregnancy, CMV can increase the risk for neurodevelopmental disabilities, and that includes things like microcephaly, deafness, and learning disabilities. Obviously, what has come to more attention recently is the Zika virus, which, similar to CMV, has a direct effect on brain development. It's been less prevalent in the United States but is definitely prevalent in the Americas. Zika virus can also lead to a spectrum of neurodevelopmental outcomes.

The role of an immune response is one that we know less about, but it's definitely a subject of investigation currently. We know that any sort of fever or infection—influenza, upper respiratory infections, any sort of bacterial or fungal infection—that causes an immune response or a fever during pregnancy causes an inflammation response and a cascade of biological events that may have an effect on brain development and potentially an increased risk for autism.

That also ties to the concept of epigenetics and how things like a fever or an immune response may modify the genes and increase the risk for autism.

Medscape: Would that altered immune response be implicated with an autoimmune condition? Is there any evidence that autoimmune conditions are linked with ASD risk?

Dr Gordon-Lipkin: That is also an emerging area of interest. The research that looks at infectious immune responses and autoimmune responses does overlap. There is some evidence that having a mother with an autoimmune disease is associated with an increased risk for ASD.

Medscape: Maternal lifestyle factors—nutrition, alcohol, smoking—have been studied also. What do we know?

Dr Gordon-Lipkin: We know that neurodevelopmental disabilities in general can be linked to things like alcohol consumption and fetal alcohol spectrum disorder. We know that maternal smoking puts children at increased risk for neurodevelopmental disability. Interestingly, autism is not specifically linked to both of those factors, but neurodevelopmental disabilities, in general, are.

In terms of other lifestyle factors, such as nutrition, there are no specific diets linked to risk for autism. However, there is some general dietary advice that should be given. For example, foods rich in folic acid are important during pregnancy because folic acid is tied to good brain development. Avoiding certain toxins in food, like mercury, is also important to decrease the risk for injury to brain development.

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