Two studies show autism risk may span multiple generations

Megan Brooks

For women who were abused in childhood and for men who fathered children in later life, the risk for autism in children and grandchildren, respectively, appears to be increased, 2 new studies suggest.

In the first study, investigators at the Harvard School of Public Health in Boston, Massachusetts, found that exposure to abuse was associated with increased risk for autism in children in a "monotonically increasing fashion."

The second study, by researchers at the Karolinska Institutet in Stockholm, Sweden, showed a statistically significant association between advancing grandparent age at the time of birth of the parent and risk for autism in grandchildren, suggesting that the risk for autism could span generations.

Both studies were published online March 20 in JAMA Psychiatry.

Maternal Abuse
In the first study, Andrea L. Roberts, PhD, and colleagues used the Nurses' Health Study II to examine the link between maternal exposure to child abuse and autism risk in offspring.

Participants included 451 mothers of children with autism and 52,498 mothers of children without autism.

"Adverse perinatal circumstances have been associated with increased risk for autism in offspring. Women exposed to childhood abuse experience more adverse perinatal circumstances than women unexposed, but whether maternal abuse is associated with autism in offspring is unknown," they write.

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The highest level of abuse was associated with the greatest prevalence of autism (1.8% vs 0.7% among women not abused, P = .005) and with the greatest risk for autism adjusted for demographic factors (risk ratio, 3.7; 95% confidence interval [CI], 2.3 - 5.8).

Adjusting for perinatal factors only slightly attenuated the link between maternal childhood abuse and autism in offspring (risk ratio for highest level of abuse, 3.0; 95% CI, 1.9 - 4.8).

Dr. Roberts said it is "important to keep in mind that only 1 in 50 of the women who experienced the most severe abuse had a child with autism, while 49 of the 50 did not."

"Because we don't yet understand why women who experienced abuse are more likely to have a child with autism, it's a little early to say there are clinical implications for preventing autism," she told Medscape Medical News.

Reached for comment, Richard E. D'Alli, MD, chief of the Division of Child Development and Behavioral Health from Duke Medicine in Durham, North Carolina, who was not involved in the study, cautioned that the study does not "move the science forward."

"This is one of those studies that mines a gigantic maternal child database, and if you look hard enough, you are going to find a pattern. Also, if you look at the abused population of women, there's a lot of other stuff going on," such as use of selective serotonin reuptake inhibitors and substance abuse, which might also be risk factors, said Dr. D'Alli.

"We've come to the clinical understanding," he added, "that this is fundamentally a brain wiring defect, it's genetic programming gone awry, with possible genetic programming that is pushed over the edge" by environmental factors.

Yet, to separate this out is very difficult.

"I'm not sure a woman who is abused has anything to do with the ultimate way that the brain is wired up, and there are so many women who are abused who don't have autistic kids," he added.

Consequences of Waiting?
In the second study, investigators used multigeneration and patient registries to build on knowledge about the link between parental age and autism by studying the effect of grandfathers' age on childhood autism.

"In this study, we could not only replicate the previously found link between paternal age and autism in the child, but we also show that older men have an increased risk of having a grandchild with autism," Emma Frans, of the Karolinska Institutet, told Medscape Medical News.

+ More: 5 tips for a happy future for kids with autism

Participants included 5936 individuals with autism and 30,923 individuals without autism. The researchers determined the age of each individual's maternal and paternal grandfather at the time of the individual's birth.

After controlling for potentially confounding factors, in comparison with men who had fathered children in their early 20s, men who had fathered a daughter at age 50 years or older were 1.79 times (95% CI, 1.35 - 2.37; P < .001) more likely to have a grandchild with autism, and men who had fathered a son at this age were 1.67 times more likely (95% CI, 1.35 - 2.37; P < .001).

The study also confirms a statistically significant association between advanced paternal age and an increased risk for autism in offspring, as reported previously by Medscape Medical News.

"Sensitivity analyses indicated that these findings were not the result of bias due to missing data on grandparental age," the investigators say.

These findings, they conclude, suggest that risk for autism "could develop over generations. The results are consistent with mutations and/or epigenetic alterations associated with advancing paternal age."

"The risk of new mutations increases with paternal age. The mutations are passed on to coming generations and may therefore affect the health of both children and grandchildren," Frans told Medscape Medical News.

The investigators caution, however, that older men "should not be discouraged to have children based on these findings, but the results may be important in understanding the mechanism behind childhood autism and other psychiatric and neurodevelopmental disorders."

"We've known that maternal age is associated with decreased fertility and an increased risk for certain congenital disorders in the offspring. Only recently have studies focused on the effects of older paternal age," Frans added. "This study will hopefully increase the awareness of the risks associated with becoming a father at an older age and the consequences it has for coming generations."

Source: Medscape

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