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Researchers Confirm Link between Maternal Age and Autism

By Thaddeus Schug
March 2010

Shelton, above, was corresponding author on the paper. (Photo courtesy of Janie Shelton)

Principal Investigator Herzt-Picciotto has called for more research into the environmental causes of autism. She and colleagues at UCD are participating in the Early Autism Risk Longitudinal Investigation (EARLI) launched in June 2009. (Photo courtesy of UCD Office of Communications)

In a new NIEHS-funded study, researchers at the University of California, Davis (UCD) confirmed a link between advanced maternal age and an elevated risk of having a child with autism, regardless of the father's age.

According to the study( Exit NIEHS, which analyzed nearly five million births in California during the 1990s, the risk of having a child with autism increased by 18 percent - nearly one fifth - for every five-year increase in the mother's age over the age of 30. The study appears online in the journal Autism Research.

Revising current theory through the power of numbers

"This study challenges a current theory in autism epidemiology that identifies the father's age as a key factor in increasing the risk of having a child with autism," said Janie Shelton, the study's lead author and a doctoral student in the UCD Department of Public Health Sciences. "It shows that while maternal age consistently increases the risk of autism, the father's age only contributes an increased risk when the father is older than 30 and the mother is under 30 years old. Among mothers over 30, increases in the father's age do not appear to further increase the risk of autism."

Autism is a pervasive developmental disorder of deficits in social skills and communication, as well as repetitive and restricted behaviors, with onset occurring prior to age 3. Abnormal brain development, most likely beginning in the womb, is known to be fundamental to the behaviors that characterize autism.

Because of the large study size, researchers were able to show how risk for autism was affected by each parent's age by holding one parent's age constant and then examining the risk associated with five-year increases in the other parent's age. The subtle interaction of how each parent's age increases the risk of autism allowed the researchers to identify different effects from maternal and paternal age. This methodology is effective at teasing out effects of highly correlated variables (mother's and father's age) and was only possible with an extremely large dataset, according to the researchers.

The researchers also used the power of their large study to revise another assumption - that the dramatic rise in incidence of autism during the 1990s could be explained by the 300 percent increase in the number of California women over 40 giving birth. As Shelton explained, "We found only about five percent of the increase could be attributed to trends toward older mothers," suggesting other factors, such as environmental exposures, are more significant.

Increased parental age may foster changes in fetal gene expression

The researchers note that understanding the relationship between increased parental age and autism risk is critical to understanding its biological causes. Earlier studies cited by the authors observed that advanced maternal age is a risk factor for a variety of other birth-related conditions, including infertility, early fetal loss, low birth-weight, chromosomal aberrations, and congenital anomalies.

Senior author Irva Hertz-Picciotto, Ph.D.( Exit NIEHS, a UCD professor of epidemiology and preventive medicine, said the reason that having an older parent places a child at risk for autism is not known. "We still need to figure out what it is about older parents that puts their children at greater risk for autism and other adverse outcomes, so that we can begin to design interventions."

The authors suggest that epigenetic changes over time may enable an older parent to transfer a multitude of molecular functional alterations to a child. Environmental exposures independent of one's genetic makeup can lead to histone modifications and alter methylation patterns, which can ultimately affect gene expression patterns in subsequent generations. Thus, they conclude, "Epigenetics may be involved in the risks contributed by advancing parental age as a result of changes induced by stresses from environmental chemicals, co-morbidity, or assistive reproductive therapy."

Citation: Shelton JF, Tancredi DJ, Hertz-Picciotto I.( Exit NIEHS 2010. Independent and Dependent Contributions of Advanced Maternal and Paternal Ages to Autism Risk. Autism Res (3). Epub ahead of print. DOI: 10.1002/aur.116

(Thaddeus Schug, Ph.D., is a postdoctoral research fellow in the NIEHS Laboratory of Signal Transduction.)

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