A large new study finds that maternal diabetes during pregnancy—particularly type 1 diabetes, the disease’s rarest form—is associated with a significant increase in the risk that a child will later develop autism. The study is a continuation of previous research linking a mother’s diabetes to autism, its authors say, but was among the first to account for the effect of both type 1 and type 2 diabetes on a large scale.
“People have been studying [the relationship between maternal diabetes and autism] for many years,” says lead author Anny Xiang, Director of Biostatistics Research at the Kaiser Permanente Department of Research and Evaluation. “This is the first study to examine type 1 diabetes”—likely because the condition is “still very rare,” she adds, accounting for only about 5 percent of diabetes cases in the U.S. Type 1 diabetes is an autoimmune disorder, most often diagnosed in childhood, in which the body is unable to produce adequate levels of insulin. Type 2 diabetes is typically diagnosed later, and develops when the body becomes resistant to insulin, usually due to genetic or lifestyle factors.
The study, published earlier this month in JAMA, examined medical records from nearly 420,000 children born in Kaiser Permanente hospitals in Southern California between 1995 and 2012. Of the sample, 621 were born to mothers with type 1 diabetes, 9,453 had mothers with type 2 diabetes, and 36,427 were exposed to gestational diabetes—a type that develops only during pregnancy and impacts approximately 2 to 10 percent of pregnant women. Doctors typically test for gestational diabetes between 24 and 28 weeks of pregnancy—earlier if the mother is deemed to be at high risk. The majority of gestational diabetes cases in the study were diagnosed after 26 weeks of pregnancy. All mothers with type 1 or type 2 took diabetes medication during their pregnancy; mothers with gestational diabetes were only given medication if they struggled to control their glucose levels with diet and exercise, Xiang says.
By the study’s conclusion in 2017, children who had been exposed to type 1 diabetes in utero had been diagnosed with autism at rates of 4.4 per 1,000, compared to 1.8 per 1,000 for children who hadn’t been exposed to diabetes at all. The results also affirmed the findings of a previous study of maternal type 2 and gestational diabetes by the same researchers. In the current study, they identified rates of autism diagnosis as 3.6 per 1,000 for type 2 diabetes, 2.9 per 1,000 for gestational diabetes diagnosed before 26 weeks, and 2.1 per 1,000 for gestational diabetes diagnosed later than 26 weeks. The use of diabetes medication in the gestational diabetes group did not significantly impact autism rates.
Though the study controlled for other potential risk factors, such as smoking during pregnancy, maternal obesity (which has also been linked to autism in the past) or socioeconomic factors, it was still only observational, Xiang says, and the reason for the link between diabetes and autism is not yet established.
“It could be that the mom has inflammation associated with diabetes,” she says. “It could be high or low glucose levels causing stress to the baby during pregnancy.” Since the risk was lessened for children whose mothers had gestational diabetes later in their pregnancy, it stands to reason that the effect is strongest during the early periods of a baby’s development, she says.
Annette Estes, director of the Autism Center at the University of Washington, thinks that the inflammation theory may be closest to the truth.
“The inflammation hypothesis is an active one right now in autism research,” says Estes, who wasn’t involved in the study. “Very early on [in the study of autism] there was a finding of increased cerebral volume in kids with autism,” which was hypothesized to be the result of brain inflammation, she says. Brain development happens rapidly in the first 26 weeks of gestation, with the most dramatic changes happening around week 23, Estes explains. “Anything that alters brain development can be considered as a potential risk factor for autism.”
Though both Xiang and Estes encourage mothers at risk for diabetes to be screened regularly—and treated appropriately, as untreated diabetes poses additional risks to the developing fetus—the overall risk of their child later developing autism remains small.
“It’s always really important for mothers to get high-quality healthcare when they’re pregnant,” Estes said. “This isn’t specific to autism—[this study] just underscores the fact that good prenatal care is important for everyone to have access to.” And since the study doesn’t establish a causal effect—and because other risk factors, like genetics, could also be at play—the risk of a mother with diabetes giving birth to a child with autism shouldn’t be overstated, she said. “This study is more important for researchers to understand the root causes of autism,” she says. “It’s pointing us towards research that’s more prospective in nature.”