Maternal Diabetes and the Risk of Autism Spectrum Disorders in Offspring

Early screening in mothers with diabetes may be help to reduce ASD risk in children…

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Children born to mothers with diabetes or gestational diabetes mellitus (GDM) may be affected in many different ways. Studies have shown that these long-term risks include obesity, related metabolic disorders, and possibly abnormal fetal brain development, and neurobehavioral developmental disorders. Autism spectrum disorders (ASD) are neurodevelopmental disorders that affect social interaction and communication with restricted and repetitive behaviors. Meta-analyses have shown a link between exposure to maternal diabetes and higher risk of ASD in children. However, not much research has been done on the association between GDM and ASD risk. Researchers from Kaiser Permanente Southern California (KPSC-Pasadena), Keck School of Medicine – University of Southern California (Los Angeles), and the Rutgers–Robert Wood Johnson Medical School (New Brunswick, New Jersey) assessed and analyzed the association between maternal diabetes, both known before and during pregnancy, and the risk of ASD in offspring in a recent study.

This retrospective longitudinal cohort study included 322,323 children born at 28 to 44 weeks’ gestation in KPSC hospitals between January 1, 1995 and December 31, 2009. Exclusion criteria included children who were born to mothers with type 1 diabetes, those with congenital anomalies, and those not enrolled as KPSC plan members by 1 year old. The child behavior questionnaires and brief screening checklist were given to screen for developmental delays, including ASD. The exposure variable was maternal type 2 diabetes or maternal GDM during pregnancy. Outcome measures were the age and presence or absence of ASD during follow-up. Equivalent name for ASD included autistic disorders, Asperger syndrome, or pervasive developmental disorder not otherwise specified (PDD-NOS), and excluded childhood disintegrative disorder and Rett syndrome. Covariates to control for potential confounding were maternal age at delivery, parity, education, self-reported maternal race/ethnicity, median family household income based on census tract of residence, history of comorbidity (≥1 diagnosis of heart, lung, kidney, or liver disease; cancer), and sex of the child. Statistical tests included Chi-squared test and ANOVA.

Among all children enrolled, 3388 children were diagnosed with ASD (115 exposed to pre-existing type 2 diabetes, 130 exposed to GDM at ≤26 weeks, 180 exposed to GDM at >26 weeks, and 2963 unexposed). Unadjusted annual ASD incidences were 3.26, 3.02, 1.77, and 1.77 per 1000 among children of mothers with pre-existing type 2 diabetes, GDM diagnosed at 26 weeks or earlier, GDM diagnosed after 26 weeks, and no diabetes, respectively. The birth year–adjusted HRs were 1.59 (95% CI, 1.29-1.95) for pre-existing type 2 diabetes, 1.63 (95% CI, 1.35-1.97) for GDM diagnosed at 26 weeks or earlier, and 0.98 (95% CI, 0.84-1.15) for GDM diagnosed after 26 weeks relative to no exposure. After adjustment, maternal with pre-existing type 2 diabetes was not linked with ASD in children (HR, 1.21; 95% CI, 0.97-1.52). However, GDM diagnosed at 26 weeks or earlier was associated with higher risk of ASD (HR, 1.42; 95% CI, 1.15-1.74). Additionally, anti-diabetic medication was not associated with ASD risk.

In conclusion, exposure to maternal GDM diagnosed by 26 weeks’ gestation was associated with higher risk of ASD in children. Thus, early screening for ASD in children of mothers with GDM diagnosed by 26 weeks’ gestation is necessary to reduce ASD risk.

Practice Pearls:

• Exposure to maternal GDM diagnosed by 26 weeks’ gestation was associated with higher risk of ASD in children.
• Early screening for ASD in children of mothers with GDM diagnosed by 26 weeks’ gestation is necessary.
• Further researches are necessary to determine if early screening can reduce the risk of ASD.

 Xiang et al. "Association of Maternal Diabetes With Autism in Offspring." JAMA. 2015;313(14):1425-1434.