Maternal HbA1c Influences Autism Risk in Offspring

Epidemiologic data suggest that maternal diabetes influences the risk for autism in offspring, whereas the prevalence of autism has steadily risen in the USA, currently affecting 1 in 59 children, and boys are four to five times more likely to receive an autism diagnosis.

According to a comprehensive survey children born to women with glycated hemoglobin (HbA1c) level of at least 6.5% were nearly twice as likely to receive a diagnosis of autism in the first four years of life versus offspring of mothers with HbA1c below 5.7%.

Scientists carried out a retrospective study and analyzed electronic medical records data from 35,819 mother-infant pairs (51% boys) born in hospitals connected to Kaiser Permanente Southern California (Pasadena, CA, USA) from 2012 to 2013 (maternal mean maternal age, 31 years; mean pre-pregnancy BMI, 27.2 kg/m²; 51% Hispanic). The team followed the children until they received a diagnosis of autism with at least one diagnostic code or December 31, 2017. The last maternal HbA1c level in the first two trimesters of pregnancy was obtained from the electronic laboratory database. HbA1c was analyzed as a continuous variable and a categorical variable, classified as less than 5.7%, 5.7% to 5.9%, 6% to 6.5%, and greater than 6.5%.

Within the cohort, 84.9% of mothers had an HbA1c less than 5.7%; 11.7% had an HbA1c between 5.7% and 5.9; 2.4% between 6% and 6.5%; and 1% greater than 6.5%. During a median follow-up of 4.5 years, 707 children (2%) had a clinical diagnosis of autism. After adjusting for pre-pregnancy BMI and race, the Hazard Ratio (HR) for autism associated with each 1% increase of HbA1c level was 1.12 (95% CI, 0.96-1.31) for the continuous measure. Compared with children with a maternal HbA1c of less than 5.7%, children born to women with an HbA1c greater than 6.5% were nearly twice as likely to receive a diagnosis of autism during follow-up (HR = 1.79; 95% CI, 1.06-3).

Anny H. Xiang, PhD, director of biostatistics for Kaiser Permanente Southern California, said, “Maternal diabetes, if not well treated, which means hyperglycemia in utero, that increases uterine inflammation, oxidative stress and hypoxia and may alter gene expression. This can disrupt fetal brain development, increasing the risk for neural behavior disorders, such as autism.” The study was presented at the American Diabetes Association 79th Scientific Meeting held June 7-11, 2019, in San Francisco, CA, USA.

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Kaiser Permanente Southern California