http://www.medpagetoday.com/Neurology/Autism/37987

Autism Linked to Parents, Grandparents

By Michael Smith, North American Correspondent, MedPage Today

Published: March 20, 2013

Reviewed by Zalman S. Agus, MD; Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania

Multigenerational factors may play a role in the incidence of autism, according to U.S. and Swedish researchers.
Mothers who experienced various forms of abuse in childhood had an increased risk of having an autistic child, according to Andrea Roberts, PhD, of the Harvard School of Public Health, and colleagues.
And men who were 50 or older when one of their children was born were more likely to have a grandchild with autism, according to Emma Frans, MSc, of the Karolinska Institutet in Stockholm, and colleagues.
The studies, both online in JAMA Psychiatry, appear as the CDC is reporting an increased prevalence of parent-reported autism, driven by recent diagnoses among children with previously unrecognized disorders.
The etiology of autism isn't known, Roberts and colleagues noted, but many hypotheses focus on the perinatal period and such things as low birth weight, prematurity, and gestational diabetes.
Mothers who experienced abuse in childhood have more perinatal adverse circumstances, they added, but it is not clear if that influences their risk of having an autistic child.
To help clarify the issue, they turned to the Nurses' Health Study II, a population-based longitudinal cohort of 116,430 women that began in 1989. Participants have been followed with questionnaires every 2 years.
For this analysis, Roberts and colleagues looked at data from a subset of nearly 55,000 women who reported if they had a child with any autism spectrum disorder and who also answered a questionnaire about abuse in childhood.
The researchers stratified participants into four groups on the basis of reported physical and emotional abuse, from none to most severe, and did the same thing with sexual abuse. They also created a combined score by adding up the physical and emotional abuse and sexual abuse measures.
Overall, 451 mothers reported children with autism and 52,498 participants did not, Roberts and colleagues reported.
They found:

The highest level of combined abuse was significantly associated (at P=0.005) with the greatest prevalence of autism, compared with women who reported no childhood abuse -- 1.8% versus 0.7%.
Adjusted for demographic factors, the highest level of abuse was associated with a risk ratio for autism of 3.7 (95% CI 2.3 to 5.8).
Except for low birth weight, adverse perinatal circumstances were more common among women abused in childhood.
When the researchers adjusted for perinatal factors, the association was attenuated but only slightly – the risk ratio became 3.0 (95% CI 1.9 to 4.8) when comparing the highest abuse level with none.

Perinatal factors accounted for only a small part of the risk of autism in offspring, but Roberts and colleagues cautioned that unmeasured factors might also play a role.
They also cautioned that autism and abuse in the study were self-reported, which might have introduced bias.
In the Swedish study, Frans and colleagues noted that advancing paternal age has been linked to autism in offspring. Indeed, one recent study on people with sporadic schizophrenia or autism found a high annual rate of new mutations in relation to paternal age.
Using the country's population-based longitudinal registers, they compared the ages of parents and grandparents at the birth of a child with or without a childhood autism diagnosis.
They were able to get parental age at birth for more than 90% of the cohort, but only able to get age of grandparents at the time of birth of the parent for 5,936 cases and 30,923 controls.
In logistic regression analyses, the risk of autism "increased monotonically" with advancing age of the grandfather, the researchers found. Specifically:

Men who fathered a daughter when they were 50 or older – compared with those who had children when they were 20 to 24 – had an adjusted odds ratio for an autistic grandchild of 1.79 (95% CI 1.35 to 2.37, P<0 .001="" li="">
Similarly, men who had fathered a son when they were 50 or older had an odds ratio for an autistic grandchild of 1.67 (95% CI 1.35 to 2.37, P<0 .001="" li="">

The findings imply that the risk of autism is multigenerational, Frans and colleagues argued, and "are consistent with mutations and/or epigenetic alterations associated with advancing paternal age."
"Older men should not be discouraged to have children based on these findings," they concluded, "but the results may be important in understanding the mechanism behind childhood autism and other psychiatric and neurodevelopmental disorders."

The study by Roberts et al. had support from the Department of Defense, the US Army Medical Research and Materiel Command, and the NIH.
The journal said the authors made no disclosures.
The study by Frans et al. was supported by the Swedish Research Council, the Swedish Council for Working Life and Social Research, and the Karolinska Institutet.
The journal said the authors made no disclosures.

Primary source: JAMA Psychiatry
Source reference:
Roberts AL, et al "Association of maternal exposure to childhood abuse with elevated risk for autism in offspring" JAMA Psychiatry 2013; DOI: 10.1001/jamapsychiatry.2013.447.
Additional source: JAMA Psychiatry
Source reference:
Frans EM, et al "Autism risk across generations: A population-based study of advancing grandpaternal and paternal age" JAMA Psychiatry 2013; DOI: 10.1001/jamapsychiatry.2013.1180.Autism Linked to Parents, Grandparents