Autism Spectrum Disorders and Maternal Lifestyle: Talking About Glucose

Silvia Hoirisch-Clapauch, MD, PhD, of the Hospital dos Servidores do Estado do Rio de Janeiro, Brazil, presented a talk at the Annual Meeting of the American Psychiatric Association in San Diego on a study linking autism spectrum disorder (ASD) to maternal lifestyle, specifically dietary factors impacting glucose levels in the mother and fetus.

Hoirisch-Clapauch began her talk with a slide illustrating the well-known action of tissue plasminogen activator (TPA) in the cleavage of plasminogen to form plasmin. Regarding the rationale for the study, she told the audience. “TPA has an important role in proteolysis. TPA is inhibited by plasminogen activator inhibitor (PAI). The PAI promoter responds to insulin and to glucose.”

Hoirisch-Clapauch described the study and its results, “Patients were recommended to walk daily and were also recommended to avoid high-carbohydrate food. We expected that this would increase the weight of take-home babies, but we were not expecting reports of intelligent offspring in the group with lifestyle modification, and the high prevalence of ASD and learning disabilities in the control group.”

She asked the audience, “Is this a link?” She next told the audience that ASD is characterized by white matter disconnectivity. “It’s not low connectivity, it’s chaotic connectivity.” Drawing an analogy with uncooked (parallel organization) and cooked (chaotic organization) spaghetti, Hoirisch-Clapauch said, “Imagine pasta. Instead of migrating parallel, the neurons migrate chaotically.” She said that Reelin, an extracellular signaling molecule, is responsible for guiding neurons, “And guess what? Reelin is activated by TPA, so low TPA levels will prevent Reelin from acting. So here is the first link, but there are other links.”

Regarding other links between maternal hyperglycemia and ASD in offspring, Hoirisch-Clapauch continued, “Hyperglycemia increases levels of neurotoxins that are harmful to the developing brain. Hyperglycemia induces embryopathy, so offspring of mothers with diabetes have a high prevalence of defects. Hyperglycemia also increases the risk of mutation, so epigenetic mutations are seen in offspring of mothers who have hyperglycemia, and Reelin is one of the described mutations in ASD.”

As a result, Hoirisch-Clapauch said, there are a number of maternal conditions that can be easily linked to ASD, including obesity, excessive maternal weight gain, and alcohol abuse. In terms of other factors, Hoirisch-Clapauch said that stressful life events increase levels of adrenaline in the mothers, which increases their blood glucose levels, adding, “Also, stressed individuals tend to eat more carbohydrates.”

Showing data from an earlier, related study by her team, Hoirisch-Clapauch said, “Our hypothesis was that a high-carbohydrate diet and physical inactivity close to delivery would lead to fetal and neonatal hyperinsulemia that would cause neonatal hypoglycemia. We selected mothers reporting a high-carbohydrate diet close to delivery combined with a lack of physical activity. When we analyzed this together with other risk factors such as being small for gestational age or low birth weight, the only significant predictors of neonatal hypoglycemia were high-carbohydrate intake and physical inactivity. Mothers with no risk factors had zero risk of having a baby with neonatal hypoglycemia.”

Of the babies with neonatal hypoglycemia, Hoirisch-Clapauch said that 10% of them were full-term, were of appropriate size for their gestational age, and were born to mothers who were slim and nondiabetic. “The conclusion is, maybe we are not identifying all the kids with neonatal hypoglycemia, and probably this will be a risk factor for ASD. When you identify neonatal hypoglycemia, you treat it. But if neonatal hypoglycemia is not being recognized, it’s not being treated, so maybe this is a risk factor for ASD and also learning disabilities.”

Concluding her remarks, Hoirisch-Clapauch said, “A healthy maternal lifestyle is healthy, so please tell the moms they need to walk, they need to eat protein, not just carbohydrate. They must refrain from eating junk food and a lot of juices and fruits, because it may look healthy, but it is not.”