Mothers' Diabetes Linked to Risk of Autism
Researchers have identified an unusual risk for a child developing autism: his mother’s diabetes. Several studies found that pregnant women with diabetes – including the temporary kind – had a higher risk of delivering a child with autism than mothers who weren't diabetic.1, 2, 3, 13
This research is important because the rate of diabetes, like the rate of autism spectrum disorder (ASD), has been rising in recent decades. Gestational diabetes, a temporary condition that only occurs during pregnancy, affects as many as one in 11 expectant mothers. Cases of another form of diabetes, called Type 2, also have been rising and affecting pregnancies.4-5 Almost 3 percent of men and women ages 20 to 44 have diabetes, according to the U.S. Centers for Disease Control.
If not detected or controlled, diabetes can cause serious problems during pregnancy, including preeclampsia (dangerously high blood pressure), abnormally large babies, and difficult deliveries.6 The baby also may have problems with breathing or blood sugar after birth.5-6
Glorie Acevedo of Puerto Rico was shocked to learn she had gestational diabetes when she was 30 weeks pregnant with twins. Her diet was healthy, she said. "My doctor told me it was common. He said, 'It's not your fault. You have twins.'" She managed her diabetes through changes to her diet. It was completely controlled by the time her fraternal twins were born at 34 weeks. One twin, Diego, developed autism spectrum disorder, but he no longer shows any signs of it, said Mrs. Acevedo, who participates in Interactive Autism Network Research.
Who's at highest risk for gestational diabetes?
Many factors can increase a woman's risk for developing gestational diabetes. They include:
- Having twins, which doubles the risk7
- Age. Risk begins rising progressively at age 25.8
- Race and ethnicity. In the United States, Asian, Hispanic, African-American, and Native American women face a higher risk that non-Hispanic whites.9-10
- Being overweight or obese6
- Having a family history of diabetes6
During pregnancy, hormones from the placenta can interfere with the work of the mother's insulin.5 Insulin is a hormone that transports glucose (sugar) from food into cells, where it turns into energy. Someone develops diabetes when that process malfunctions and excess sugar stays in the bloodstream. Gestational diabetes usually disappears after delivery, although those mothers are at higher risk for developing Type 2 diabetes, and their children are at risk for pre-diabetes, later in life.11
The risks for Type 2 diabetes are similar to those for gestational diabetes. Both can be managed through diet and exercise, pills and/or insulin shots. In Type 1 diabetes, people are usually diagnosed in childhood and require daily injections of insulin.
What's the autism-diabetes link?
Scientists have been trying to tease out the relationship between a mother's diabetes and her child's autism in recent years.
Researchers at Kaiser Permanente Southern California examined the prenatal records of more than 322,000 mothers; almost 3,400 of their children were later diagnosed with autism. In analyzing data, they took into account other factors that could affect the results, such as a mother's age, race, ethnicity, level of education, and history of heart, lung, kidney or liver disease, or cancer. They also looked at smoking and weight in a subset of the mothers. They made those adjustments to ensure they were only calculating the effect of diabetes on autism risk.1
They found that moms diagnosed with gestational diabetes by 26 weeks of pregnancy were 42 percent more likely to have a child with autism, compared to women without diabetes.1 To put it in perspective, the risk of having a child with autism is about 1.5 percent; gestational diabetes raises the risk to a little over 2 percent, according to that study.
Interestingly, women who were diagnosed with diabetes after 26 weeks of pregnancy did not have a higher risk of having a child with ASD. Perhaps that is because those children were exposed to high blood sugar after a period of critical brain development had passed, or because their mothers' diabetes was mild, the researchers speculated.1 In the United States, most doctors screen pregnant women for diabetes between their 24th and 28th week of pregnancy because that is when gestational diabetes usually develops.
What about other forms of diabetes?
The same lead researcher, biostatistician Anny Hui Xiang, PhD, studied mothers with Type 1 and Type 2 diabetes in a later study about autism risk in their babies. Her team looked at more than 400,000 children delivered at Kaiser Permanente Southern California hospitals from 1995 through 2012. Children born to mothers with Type 1 or Type 2 diabetes while pregnant with them had a higher risk of being diagnosed with autism than children whose moms did not have any form of diabetes. Dr. Xiang's group again found a higher autism risk with gestational diabetes diagnosed by 26 weeks of pregnancy. Gestational diabetes is more common in pregnant women than either Type 1 or Type 2 diabetes.16
What happens when a mother has obesity and diabetes?
Across the country, researchers launched two similar diabetes-autism studies, but with a few crucial differences. One group studied a group of mothers in Boston with a higher rate of obesity and diabetes than average.2 Being obese raises the risks of developing Type 2 diabetes12 and gestational diabetes.6
"The global epidemics of obesity and diabetes affect all ages, including pregnant women," said Xiaobin Wang, MD, one of the researchers. They wondered: Did having both conditions produce a combined effect that was greater than having just diabetes or obesity alone?
It did. According to this study, mothers who had diabetes and obesity before pregnancy were four times more likely to have a child with autism. Moms who had obesity and gestational diabetes were three times more likely to have a child with ASD. The Boston study was smaller than the one from Kaiser Permanente. Researchers analyzed the pregnancies of 2,734 women; 102 of their babies eventually were diagnosed with autism.2
The majority of those women were low-income, black or Hispanic. Do the results apply to mothers in other economic, racial or ethnic groups? "Maybe," said Dr. Wang, a professor at the Johns Hopkins Bloomberg School of Public Health. "The association between diabetes and ASD was seen across many studies of different populations," she said.
For example, an international research group reviewed 12 different studies from the United States, Canada, Australia, Sweden, and Egypt. They concluded that maternal diabetes is "significantly associated with a greater risk of ASD in the offspring."13
Another study, conducted in Cincinnati, Ohio, reached similar conclusions when examining both obesity and diabetes during pregnancy. This large study involved children seen by developmental pediatricians at Cincinnati Children's Hospital, as well as thousands of children without developmental conditions born in the same region.3 Expectant mothers who were obese or who had gestational diabetes were 1.5 times more likely to have a child with autism than other mothers in the study. Having both diabetes and obesity doubled the risk of autism in babies.3
What do these autism-diabetes studies prove?
Do these studies prove that diabetes, especially when combined with obesity, causes autism in some babies?
One of the mantras of science is that correlation (meaning a link or an association) does not equal causation. But discovering a correlation can be the first step in proving a cause and effect. One important factor in establishing a cause and effect is whether there's a scientific reason why something, in this case diabetes, might cause, contribute to, or trigger autism.
"Research is uncertain as to how, but theories include hyperglycemia [high levels of blood sugar] in the mother," explained Svena Julien, MD, assistant professor of gynecology and obstetrics at Johns Hopkins Medicine in Baltimore. "Glucose is toxic to many tissues, including the developing fetal brain.”
To combat damage caused by high sugar, Dr. Julien explained, the body releases other substances that cause inflammation, which itself is potentially harmful. Having excess body fat, which sometimes goes along with diabetes, also can create chronic inflammation, according to some researchers.13
Besides triggering inflammation, diabetes also could reduce the amount of oxygen a fetus gets.14 In short, diabetes influences the levels of insulin, oxygen, and inflammation in the womb, changing the environment in which the fetal brain is forming, Dr. Xiang's research group theorized.
Diabetes could affect the fetus through another avenue: oxidative stress. "Oxidative stress occurs during normal metabolism," the body’s process of using food and water, Dr. Julien said. "Certain substances undergo chemical reactions, and the by-products of those reactions release what are called free radicals. These substances can damage tissues and cells and lead to cell death,” she explained. A person’s antioxidants work to keep the free radicals in check. However, diabetes knocks that balance out of whack, raising the risk of oxidative stress.
Reducing risk before and during pregnancy
More research needs to be done to "determine if there is a true cause and effect" between a mother’s diabetes and her child’s autism, Dr. Julien said. Nonetheless, she and several researchers said, it's important to be aware of diabetes before and early in pregnancy, and, if diagnosed, to manage it properly.
Dr. Wang noted that obesity and diabetes can lead to complications in pregnancy, beyond a risk of autism. It's important to prevent obesity and diagnose diabetes early, "ideally before conception," she said.
A woman who is obese, has had gestational diabetes before, or has a strong family history of diabetes, could have her blood glucose levels tested before pregnancy and early in pregnancy, Dr. Julien said. Treatment early in pregnancy gives diabetic women and those at risk "the best chances to decrease the risk of autism," she said.
|Study||Population Studied||Factors Examined||Results|
|Kaiser Permanente1||322,323 children, 3,388 with ASD, in Southern California||Type 2 and gestational diabetes (GD)||42% risk increase for ASD when GD diagnosed by 26 weeks, no ASD increase for Type 2 or later onset of GD|
|Boston Birth Cohort2||2,734 children, 102 with ASD, from low-income minority population in Boston, Mass.||Pre-pregnancy diabetes (type not specified) and gestational diabetes, plus obesity||Obese mothers with diabetes three to four times more likely to have child with ASD|
|Cincinnati Children's Hospital3||38,810 control children, 503 kids with ASD, 1,533 kids with developmental delay in Cincinnati, Ohio, area||Obesity and gestational diabetes||Mothers with obesity or GD were 1.5 times more likely to have a child with ASD than controls. Having both diabetes and obesity doubled the ASD risk|
|Meta-analysis13||A review of 12 studies in 5 countries||Diabetes diagnosed before and during pregnancy||Diabetes "significantly" increases risk of autism in baby|
|Israeli study14||231,271 children born in southern Israel, of which 2409 were later hospitalized for neuropsychiatric reasons||Gestational diabetes (GD) in mothers, and neuropsychiatric hospitalizations in children||Higher risk for eating disorders (486), sleep apnea (1,347), or ASD–associated hospitalizations (32)|
|University of California15||227 mothers of 2-5 year-olds with ASD||Maternal diabetes and anti-fetal (AF) brain antibodies||In children with severe ASD, moms who had diabetes while pregnant were more likely to have AF brain antibodies.|
- Information about gestational diabetes from the U.S. National Institutes of Health and American Diabetes Association
- U.S. Centers for Disease Control's Diabetes Report Card
- Learn about IAN Research's Pregnancy and Birth Factors in ASD Survey
- Take our nonscientific poll: Did you/your mother have diabetes while pregnant?
Photos reprinted with permission of: 1) iStock, 2) Glorie Acevedo, 3) Kaiser Permanente Southern California (Dr. Xiang), 4) Johns Hopkins Medicine (Dr. Julien).
- Xiang AH, Wang X, Martinez MP,et al. (2015). ASsociation of maternal diabetes with autism in offspring doi:10.1001/jama.2015.2707
- Li, M., Fallin, M. D., Riley, A., Landa, R., Walker, S. O., Silverstein, M., . . . Wang, X. (2016). The association of maternal obesity and diabetes with autism and other developmental disabilities doi:10.1542/peds.2015-2206
- Connolly, N., Anixt, J., Manning, P., Ping-I Lin, D., Marsolo, K. A., & Bowers, K. (2016). Maternal metabolic risk factors for autism spectrum disorder-an analysis of electronic medical records and linked birth data. Autism Research : Official Journal of the International Society for Autism Research, 9(8), 829-837. doi:10.1002/aur.1586 [doi]
- DeSisto, C. L., Kim, S. Y., & Sharma, A. J. (2014). Prevalence estimates of gestational diabetes mellitus in the United States, pregnancy risk assessment monitoring system (PRAMS), 2007-2010. Prev Chronic Dis, 11, E104. doi:10.5888/pcd11.130415
- American Diabetes Association. (2014). What is gestational diabetes? Retrieved from http://www.diabetes.org/diabetes-basics/gestational/what-is-gestational-diabetes.html
- U.S. Preventive Services Task Force. (2014). Screening for gestational diabetes: Consumer guide. Retrieved from http://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/gestational-diabetes-mellitus-screening
- Rauh-Hain, J. A., Rana, S., Tamez, H., Wang, A., Cohen, B., Cohen, A., . . . Thadhani, R. (2009). Risk for developing gestational diabetes in women with twin pregnancies. The Journal of Maternal-Fetal & Neonatal Medicine : The Official Journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians, 22(4), 293-299. doi:10.1080/14767050802663194 [doi]
- Lao, T. T., Ho, L., Chan, B. C. P., & Leung, W. (2006). Maternal age and prevalence of gestational diabetes mellitus. Diabetes Care, 29(4), 948-949. doi:10.2337/diacare.29.04.06.dc05-2568
- Ferrara, A. (2007). Increasing prevalence of gestational diabetes mellitus. Diabetes Care, 30(Supplement 2), S141-S146. doi:10.2337/dc07-s206
- Dooley, S. L., Metzger, B. E., & Cho, N. H. (1991). Gestational diabetes mellitus. influence of race on disease prevalence and perinatal outcome in a U.S. population. Diabetes, 40 Suppl 2, 25-29.
- Centers for Disease Control and Prevention. (2012). Diabetes report card 2012. Retrieved from http://www.cdc.gov/diabetes/pubs/pdf/DiabetesReportCard.pdf
- Eckel, R. H., Kahn, S. E., Ferrannini, E., Goldfine, A. B., Nathan, D. M., Schwartz, M. W., . . . Smith, S. R. (2011). Obesity and type 2 diabetes: What can be unified and what needs to be individualized? doi:10.2337/dc11-0447
- Xu, G., Jing, J., Bowers, K., Liu, B., & Bao, W. (2014). Maternal diabetes and the risk of autism spectrum disorders in the offspring: A systematic review and meta-analysis. Journal of Autism and Developmental Disorders, 44(4), 766-775. doi:10.1007/s10803-013-1928-2 [doi]
- Nahum Sacks, K., Friger, M., Shoham-Vardi, I., Abokaf, H., Spiegel, E., Sergienko, R., . . . Sheiner, E. (2016). Prenatal exposure to gestational diabetes mellitus as an independent risk factor for long-term neuropsychiatric morbidity of the offspring. American Journal of Obstetrics and Gynecology, doi:S0002-9378(16)00522-6 [pii]
- Krakowiak, P., Walker, C. K., Tancredi, D., Hertz-Picciotto, I., & Van de Water, J. (2016). Autism-specific maternal anti-fetal brain autoantibodies are associated with metabolic conditions. Autism Research : Official Journal of the International Society for Autism Research, doi:10.1002/aur.1657 [doi]
- Xiang, A. H., Wang, X., Martinez, M. P., Page, K., Buchanan, T. A., & Feldman, R. K. (2018). Maternal type 1 diabetes and risk of autism in offspring. Jama, 320(1), 89-91. doi:10.1001/jama.2018.7614 [doi]