The Role of Maternal Diabetes and Related Conditions In Autism and Other Developmental Delays

Background: Recent trends indicate a rising prevalence of diabetes as well as obesity and hypertension, conditions indicative of elevated insulin resistance. These trends parallel the increasing rates of autism. Although the etiology of this disorder is unknown, studies suggest that its pathogenesis begins in utero.

Objectives: This study examined whether prenatal exposure to maternal gestational or type 2 diabetes, hypertension, and/or obesity was associated with (1) an increased risk of having a child with autism or autism spectrum disorders (AU/ASD) or other developmental delays (DD) and (2) greater impairments in cognitive development.

Methods: Data came from 1001 children (508 AU/ASD, 178 DD, and 315 typical controls [TD]) enrolled in The CHARGE (CHildhood Autism Risks from Genetics and the Environment) Study, an ongoing population-based case-control study. Maternal conditions were ascertained from medical records or telephone interview with parent. Maternal diabetes and hypertension were considered to be present if these conditions were recorded in the prenatal medical record or self-reported in a telephone interview. Obesity was defined as body mass index (BMI) ≥30.0, calculated using height and pre-pregnancy weight recorded in the prenatal medical record or via interview. Models were adjusted for mother’s education, delivery payer, calendar time, and frequency-matching variables child’s age and sex, and Regional Center catchment area.

Results: Women with diabetes, hypertension, and/or obesity had a nearly two-fold increased risk of having a child with AU/ASD or DD compared to women without these conditions (odds ratio [OR] 1.84, 95% confidence interval [CI] 1.30-2.62; OR 2.13, 95% CI: 1.37-3.30, respectively). Among children with ASD, Mullen Scales of Early Learning (MSEL) expressive language scores were significantly lower for children of mothers with diabetes compared to those whose mothers did not have diabetes (Least Squares [LS] mean 22.29, standard error [SE] 1.15 vs. LS mean 26.06, SE 0.54; P = 0.0025); no significant differences in MSEL scores were observed with other maternal conditions in the ASD group. Among children with no ASD (DD + TD), children of mothers with hypertension, compared to children of mothers without hypertension, had significantly lower MSEL fine motor (LS mean 32.52, SE 2.96 vs. LS mean 42.79, SE 0.82; P = 0.0008), receptive language (LS mean 33.89, SE 2.79 vs. LS mean 41.59, SE 0.74; P = 0.0072), and expressive language (LS mean 35.48, SE 2.50 vs. LS mean 41.55, SE 0.74; P = 0.0190). Similarly, compared to children of mothers with no conditions of interest, children of mothers with one or more conditions had significantly lower fine motor (LS mean 39.09, SE 1.52 vs. LS mean 43.47, SE 0.92; P = 0.0128), receptive language (LS mean 37.67, SE 1.37 vs. LS mean 42.50, SE 0.83; P = 0.0020), and expressive language scores (LS mean 37.61, SE 1.31 vs. 42.56, SE 0.84; P = 0.0011).

Conclusions: Our findings suggest that diabetes and other conditions indicative of elevated insulin resistance, such as hypertension and obesity, may play a role in the pathogenesis of developmental disorders.