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The Womb as Environment

July 04, 2011

It’s not just genes.

The results of the largest autism twin study ever performed suggest that environmental influences during pregnancy may significantly increase the risk for autism spectrum disorder (ASD) among twins. This contrasts with previous thinking – based on much smaller twin studies – that inherited genes, by themselves, account for virtually all of a child’s risk for developing the disorder.

“It has been well-established that genetic factors contribute to risk for autism,” says Clara Lajonchere, PhD, a study co-author and vice president of clinical programs for Autism Speaks. “We now have strong evidence that, on top of genetic heritability, a shared prenatal environment may have a greater than previously realized role in the development of autism.” The large sample size in the Stanford study was made possible by the collaboration of Autism Speaks’ Autism Genetic Resource Exchange (AGRE), which Lajonchere heads. Her clinical staff performed the home-based testing of many of the study participants, using scientifically validated research measures for diagnosing autism spectrum disorders.

“It takes a combination of genetics and shared environmental factors, and the environmental factors that twins, but not other siblings, share occur during pregnancy and the perinatal [birth] period,” adds lead researcher Joachim Hallmayer, MD, of Stanford University School of Medicine, in California. The California Autism Twins Study (CATS) will appear in the November issue of the Archives of General Psychiatry and is now online in advance of publication. 

The study involved 192 pairs of twins, both identical and non-identical, with at least one twin in each pair having autism.  This approach allows researchers to look at how often both children in a twin pair (versus just one) receive a diagnosis of autism.  Since identical twins share 100 percent of their genes, they help researchers determine the degree to which a disorder is inherited (genetic).  Given that non-identical, or fraternal, twins share around 50 percent of their DNA, comparing the two groups allows researchers to understand how environmental influences add to the genetic, or inherited, risk of a condition. 

Three much smaller, previous studies had suggested when one identical twin develops autism, the chance of the other twin developing the disorder is as high as 90 percent. These same studies showed little to no overlap among fraternal twins – leading to the conclusion that inherited genes, alone, produced the risk. 

By contrast, the Stanford study found 70 percent overlap among identical twins. More surprisingly, it documented a whopping 35 percent overlap among fraternal twins. This is considerably higher than the 3 percent to 14 percent overlap among different-age siblings and, so, suggests that the environmental influences involved may be uniquely shared by twins. This, in turn, is focusing attention on conditions in the womb.

Indeed, twinning itself may well be a risk factor for autism, comments McMaster University child psychiatrist and epidemiologist Peter Szatmari, a leader in the autism research field who was not involved in the study. “Perhaps ASD can be considered, at least in part, a disorder of fetal programming,” he says. “There is in fact evidence that certain risk factors that affect the maternal fetal environment may place that fetus at increased risk of ASD. Clearly a renewed effort needs to be undertaken through the use of well designed community-based epidemiologic studies”

What the study could not pinpoint was the specific time period (i.e. early pregnancy, late pregnancy or birth) nor the specific risk factors (i.e. parental age, maternal nutrition, maternal infections during pregnancy, premature and/or underweight birth, etc.) that contribute to the increased risk, Lajonchere explains. “This truly speaks to the importance of further study on what prenatal and perinatal factors increase risk beyond that of inherited genes,” she concludes. “Autism Speaks is investing in research that is exploring a wide range of environmental factors that may potentially contribute to autism risk.  The bottom line is that parents are looking to us for these answers.” For more on the study, read a blog post by Clara Lajonchere.