Study: Maternal Obesity And Diabetes Bring 'Multiple Hits,' May Raise Autism Risk In Children

A provocative new study finds that children born to mothers with a combination of obesity and diabetes before and during pregnancy may have up to four times the risk of developing autism spectrum disorder.

On their own, obesity as well as pre-pregnancy diabetes or gestational diabetes increase the risk of autism slightly, researchers report. But the study suggests that co-occurring obesity and diabetes may bring “multiple hits” to the developing fetal brain, conferring an even higher risk of autism in the offspring than either condition on its own.

According to the U.S. Centers for Disease Control and Prevention, about 1 in 68 children has autism spectrum disorder, which also includes Asperger syndrome and other pervasive developmental disorders.

This new study -- led by researchers at the Johns Hopkins Bloomberg School of Public Health and published in the journal Pediatrics -- was based on analyzing the medical records of 2,734 children who have been followed from birth at the Boston Medical Center between 1998 and 2014. (Of that group, 102 of the children had a diagnosis of an autism spectrum disorder. )

So what might be leading to this increased autism risk? Researchers don't really know, but they raise several theories in the paper. In general, the possible mechanisms relate to immune and metabolic system disturbances associated with maternal obesity and diabetes that might cause inflammation and other problems for the developing fetus.

One of the study authors, Daniele Fallin, an epidemiologist and chair of the Department of Mental Health at Hopkins' public health school, said in an interview: "We know that both diabetes and obesity create stress on the body, generally, and a lot of that stress manifests in disruption of immune processes and inflammation. Once you have the disruption in the mom, that may lead to inflammation problems in the developing fetus, and inflammation during neurodevelopment can create problems that manifest as autism."

She reiterated several possible mechanisms that may be implicated.

First, she said there's emerging evidence in autism that folate supplementation before or during pregnancy can be potentially protective.

"The reason that connects to this paper is that it's also known that obesity disrupts your ability to uptake that folic acid supplementation," Fallin said. "If that's true, whatever protective effect a mom might get from the folic acid might be undermined by her being obese or diabetic."

Also, she added, hyperglycemia related to diabetes in that the mom can create oxidative stress on the child and that puts a burden on the child's cells during development.

But, Fallin says, these remain just hypotheses.

"What we've done is shows this association, but it doesn't prove any of these theories. We need to do a lot more work to figure out which of these might truly be in play," she said, adding a bit of hope to the findings: "This points to prenatal origins of risk for autism, but it also points to prevention because these are modifiable risk factors."

In an interview, Dr. Paul Wang -- a New York-based pediatrician and vice president of medical research at Autism Speaks, an advocacy group that funds autism research -- said the new study is "important" and "advances the field ... by taking a very close look at the combined effects of obesity and diabetes, and finding that the presence of both risk factors is much more important than either one alone."

Wang said there are some weaknesses to the study, notably that it drew data from patients' medical records rather than examining the affected children directly to determine signs of autism.

He added: "It is still true that the vast majority of children whose mothers who have obesity and diabetes of every type (both before pregnancy and gestational diabetes) will not develop autism." This study, he says, finds "a moderately increased risk of three of four times" for mothers with diabetes who are also obese.

In the meantime, he said, "clearly from this and other studies, any woman thinking about being pregnant or becoming pregnant should make sure her health is as good as it can be — in terms of nutrition, weight, infection — all of these are factors can can affect risk of autism in children."

Despite the hypotheses put forth in the paper, Wang said: "We really don't know exactly how obesity and diabetes might be working to cause autism."