How much can environmental factors explain the apparent rise in autism spectrum disorders?

Roughly 1 per cent of children in the US population are affected by autism spectrum disorder (ASD). Rates in many countries, including the US, have risen sharply in recent years but no one is sure why. It is still not clear whether this is prompted by something in the environment, increased awareness of the condition and changes in diagnoses, or a result of people having children later.

The environmental case is hotly debated. There is some evidence that maternal infections during pregnancy can increase the risk. Other studies have pointed to a possible link with antidepressants while others have looked at elevated levels of mercury. But determining prenatal exposure to any substance is difficult because it is hard to know what substances people have been exposed to and when.

To get around this, Andrey Rzhetsky and colleagues at the University of Chicago analysed US health insurance claims containing over 100 million patient records – a third of the population – dating from 2003 to 2010. They used rates of genital malformations in newborn boys as a proxy of parents’ exposure to environmental risk factors. This is based on research linking a proportion of these malformations to toxins in the environment, including pesticides, lead and medicines.


Toxic environment?

The team compared the rates of these malformations to rates of ASD county by county. After adjusting for gender, income, ethnicity and socio-economic status, they found that a 1 per cent increase in birth defects – their measure for environmental effects – was associated with an average increase of 283 per cent in cases of ASD.

Rates of autism were several times greater in some counties than others, which the researchers interpret as being the result of environmental toxins.

“If toxins are driving the geographic variation in autism incidence, there are practical implications,” says Rzhetsky. “Parents should pay attention to their kids’ environment, policy-makers should clean our environment, and scientists should incorporate data about children’s environment in future genetic studies.”

However, not everyone is convinced. Dorothy Bishop at the University of Oxford points out that both genetic and environmental factors can influence rates of malformations. “I find the equating of rates of malformation with environmental causes quite worrying,” she says.

Alternative explanations

Rzhetsky counters that the clustering of malformations is harder to explain in terms of genetics. “Given how much the US population moves around and mixes, it seems unlikely that some counties would have several times as many genetic defects as others,” he says.

However, the variation across counties might also be due to differences in standards of medical care, says Benjamin Neale at the Broad Institute in Massachusetts, leading to more cases being picked up in some areas than in others.

What’s more, David Skuse at University College London points out that because the study used insurance claims the sample is not random. For instance, if someone has a genital malformation as well as ASD, it might increase their chance of making a claim. “There are all sorts of potential biases,” he says.

“There’s clearly value in analysing these large datasets, but interpretation is challenging when it’s not done in a controlled research setting,” says Neale. “I wouldn’t bet against the stance that fetal exposure to toxic compounds is bad for development, but by itself, this study does not give us a clear picture of the extent to which these environmental risk factors contribute to autism.”

Journal reference: PLoS Computational Biology, doi.org/rxd