Hormonal imbalance during pregnancy tied to autism risk

Having polycystic ovary syndrome (PCOS), a hormonal disorder that affects up to 15 percent of women of childbearing age, increases the risk of having a child with autism by 59 percent¹. The risk for obese women with the disorder is higher still — about double that of women who do not have PCOS.

The study, published 8 December in Molecular Psychiatry, is the first to finger PCOS in autism risk. Women with PCOS tend to have small cysts on the ovaries and elevated blood levels of testosterone and other male hormones, or androgens, which can lead to irregular menstrual cycles, excess body hair and infertility.

The findings fit with the controversial theory that overexposure to testosterone in the womb may raise the risk of autism.

“We found a subtly increased risk,” says lead investigator Renee Gardner, assistant professor of public health sciences at the Karolinska Institute in Stockholm, Sweden. “We can’t say that it really is the androgens causing it, but it’s another piece of evidence that fits in with that particular puzzle.”

Still, the absolute risk remains low, Gardner says. She estimates that only about 3 percent of women with the disorder will have a child with autism, compared with about 2.5 percent in the general population.

Hormone hint:

Using the Swedish National Patient Register, a repository of medical records that includes psychiatric diagnoses, Gardner and her team identified 23,748 people with autism and 208,796 people without the condition born between 1984 and 2007. They obtained information about each individual’s mother from the country’s Medical Birth Register.

After controlling for parental age, education, income and history of psychiatric illness, Gardner and her colleagues found that children born to women with PCOS are 1.59 times more likely to have autism than those born to women without the disorder. The risk is the same for boys and girls.

The link between maternal PCOS and autism held up when the researchers accounted for additional factors that may increase autism risk, such as gestational diabetes, low birth weight, premature birth and high blood pressure in the mother. It also persisted when the researchers took into account the use of infertility treatments, which have more tenuous ties to autism risk.

Obesity link:

The women with PCOS in the study were more likely than controls to be overweight or obese. Because obesity during pregnancy has been independently linked to autism, Gardner’s team examined the relationship between PCOS, body weight and the risk of bearing a child with autism in the women for whom they had body mass data. This group included the mothers of 16,377 people with autism and 117,279 controls.

When the researchers controlled for differences in maternal body mass, they found that children born to women with PCOS remained at an increased risk of autism, although the risk fell slightly to about 1.3 times the average risk. The analysis further revealed that children born to obese women with PCOS are 2.13 times more likely to have autism than are children of controls.

The findings suggest that prenatal exposure to higher-than-normal levels of androgens boosts a child’s risk of autism. Gardner says obesity may amplify this risk because it can further raise male hormone levels. Unknown genetic factors common to both PCOS and obesity may also increase the chances of autism, she says.

But because PCOS and obesity are so intertwined, it is difficult to tease apart the contributions of each condition to autism risk, says Kristen Lyall, assistant professor in the Modifiable Autism Risk Factors Program at the A.J. Drexel Autism Institute in Philadelphia, who was not involved in the work.

To better understand the autism connection, Gardner says the next step is to get a grasp on the relationship between androgen levels in blood to those in the womb by measuring them in both places. “We need to dig down and get to the mechanisms that could be driving this association,” she says.