Intrauterine exposure to maternal gestational diabetes linked with risk of autism

Among a group of more than 320,000 children, intrauterine exposure to gestational diabetes mellitus diagnosed by 26 weeks’ gestation was associated with risk of autism spectrum disorders (ASDs), according to a study in the April 14 issue of JAMA. Maternal pre-existing type 2 diabetes was not significantly associated with risk of ASD in offspring.

Exposure of fetuses to maternal hyperglycemia may have long-lasting effects on organ development and function. Previous studies have revealed long-term risks of obesity and related metabolic disorders in offspring of women who had diabetes prior to pregnancy as well as women with hyperglycemia first detected during pregnancy (gestational diabetes mellitus [GDM]). Whether such exposure can disrupt fetal brain development and heighten risk of neurobehavioral developmental disorders in offspring is less clear, according to background information in the article.

Anny H. Xiang, Ph.D., of Kaiser Permanente Southern California, Pasadena, Calif., and colleagues analyzed data from a single health care system to assess the association between maternal diabetes, both known prior to pregnancy and diagnosed during pregnancy, and the risk of ASD in children. The study included 322,323 children born from 1995-2009 at Kaiser Permanente Southern California (KPSC) hospitals. Children were tracked from birth until the first of the following: date of clinical diagnosis of ASD, last date of continuous KPSC health plan membership, death due to any cause, or December 31, 2012.

Of the children included in the study, 6,496 (2.0 percent) were exposed to pre-existing type 2 diabetes, 25,035 (7.8 percent) were exposed to GDM, and 290,792 (90.2 percent) were unexposed. Following birth (median of 5.5 years), 3,388 children were diagnosed as having ASD (115 exposed to pre-existing type 2 diabetes, 130 exposed to GDM at 26 weeks or less, 180 exposed to GDM at more than 26 weeks, and 2,963 unexposed). After adjustment for various factors, including maternal age, household income, race/ethnicity, and sex of the child, GDM diagnosed by 26 weeks was significantly associated with risk of ASD in offspring, but maternal pre-existing type 2 diabetes was not.

The increased ASD risk was independent of maternal smoking, prepregnancy body mass index, and gestational weight gain. Antidiabetic medication use was not independently associated with ASD risk in offspring.

Women who develop gestational diabetes early in their pregnancy have a higher chance of having a child with autism than women who don’t develop the condition, a new study suggests.

Researchers found that mothers-to-be who developed gestational diabetes - high blood sugar during pregnancy in women who have never had diabetes - by their 26th week of pregnancy were 63 percent more likely to have a child diagnosed with an autism spectrum disorder (ASD) compared with women who did not have gestational diabetes at any point during their pregnancy (and who also did not have type 2 diabetes prior to pregnancy).

The finding does not mean that autism is common among children born to women who had gestational diabetes.


The study, one of the first of its kind, involved about 1,000 California children, ages 2 to 5. Researchers affiliated with the UC Davis MIND Institute looked at their mothers’ medical records and examined the association between obesity and autism. Women who were obese during pregnancy were about 67 percent more likely than normal-weight women to have autistic children, the study showed. Obese moms also faced double the risk of having children with other developmental delays.

Obesity isn’t the only risk factor found for pregnant moms in the study. Researchers also looked at prevalence of gestational diabetes and found pregnant moms with diabetes had nearly 2 1/3 times the chance of having a child with developmental delays compared with healthy mothers. Although the proportion of diabetic mothers who had a child with autism was higher, the numbers did not reach statistical significance.

The study was published online in the April 9 issue of Pediatrics.

Intrauterine exposure to maternal <a rel=gestational diabetes linked with risk of autism " align="right" /> The authors write that potential biological mechanisms linking intrauterine hyperglycemia and ASD risk in offspring may include multiple pathways, such as hypoxia (a lower-than-normal concentration of oxygen in the blood) in the fetus, oxidative stress in cord blood and placental tissue, chronic inflammation, and epigenetics (something that affects a cell, organ or individual without directly affecting its DNA).


(doi:10.1001/jama.2015.2707; Available pre-embargo to the media at Editor’s Note: This work was supported by Kaiser Permanente Southern California Direct Community Benefit Funds. All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

U.S. autism rates have increased along with obesity rates, says Dr. Daniel Coury, chief of developmental and behavioral pediatrics at Nationwide Children’s Hospital in Columbus, Ohio. He said the research suggests that may be more than a coincidence.

If mothers’ obesity is truly related to autism, it would be only one of many contributing factors, said Coury, who was not involved in the study.

What other factors have been linked to autism? Genetics, mothers’ illnesses and use of certain medicines during pregnancy are a few, according to the CDC.


Al Martinez
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The JAMA Network Journals


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