Maternal A1c Linked to Autism Risk in Children

Maternal diabetes, if not treated adequately, may increase the risk of several serious health complications in children. Epidemiologic data suggest that maternal pre-existing type 1, type 2, or gestational diabetes can influence the risk for autism spectrum disorders  (ASDs) in offspring. Hyperglycemia in utero increases uterine inflammation, oxidative stress, and hypoxia, potentially altering gene expression and disrupting fetal brain development, which increases the risk for neural behavior disorders. According to current estimates, 1 in 59 children is affected by autism and the prevalence of the disorder continues to rise steadily. 

Recent findings presented at the American Diabetes Association annual meeting further current understanding of the relationship between maternal diabetes and autism spectrum disorders in children. The latest research identifies an increased risk of autism diagnosis in the first 4 years of life in children whose mothers had HbA1c levels above 6.5% during pregnancy compared with those whose mothers had levels below 5.7%.

Hemoglobin A1c Levels During Pregnancy and Risk of Autism

Researchers from Kaiser Permanente Southern California led a retrospective cohort study in order to identify the association between maternal hemoglobin A1c levels during pregnancy and the risk of autism spectrum disorders in offspring. Their investigation, published in the Journal of the American Medical Association, was based on electronic medical records data from a cohort of 35,819 mother-infant pairs born in Kaiser Permanente Southern California hospitals from 2012 to 2013. The median gestational age at HbA1c testing was 9 weeks, as 83% of testing was conducted during the first trimester; a median HbA1c of 5.4% was reported.

Led by Dr. Anny Xiang, Director of Biostatistics Research at Kaiser Permanente Southern California, Pasadena, researchers followed the children until they received a diagnosis of autism with at least one diagnostic code or December 31, 2017. Investigators analyzed HbA1c measurements as continuous and categorical variables – classified as either less than 5.7%, 5.7% to 5.9%, 6% to 6.5%, and greater than 6.5%. Dr. Xiang and colleagues used Cox regression analyses to estimate hazard ratios for autism diagnosis in offspring with HbA1c exposure and assessed the interaction with gestational age at HbA1c testing.

Among the cohort, the majority of women (nearly 85%) had HbA1c levels of less than 5.7%, 11.7% had levels between 5.7% and 5.9%, 2.4% between 6% and 6.5%, and only 1% had levels greater than 6.5%. A total of 707 children (2%) were clinically diagnosed with autism during the median follow-up period of 4.5 years. The study found that children born to women with an HbA1c greater than 6.5% during early pregnancy were almost two times more likely to be diagnosed with autism at follow-up than those whose mothers had HbA1c levels below 5.7%.

“The early trimester seems to be critical, and this is consistent with the literature looking at the windows of vulnerability in risk for autism,” Dr. Xiang told Endocrine Today. “This is evident in pregnancies with type 1 or type 2 or gestational diabetes diagnosed early, or when HbA1c was high in the first two trimesters, but there is no association observed in the third trimester.”

Dr. Xiang’s findings underscore the importance of glycemic control in the early stages of pregnancy and beyond. All three types of maternal diabetes can have potentially detrimental health consequences in children born to women with high levels of HbA1c, ranging from hypoglycemia to an increased risk of neural behavior disorders such as autism. Women planning on becoming pregnant or those already pregnant should make sure to maintain glycemic control, treating hyperglycemia if necessary and monitoring blood sugar throughout all three trimesters.