Children exposed to GDM in utero are at increased risk of developing autism spectrum disorder, a neurodevelopmental disorder characterized by social deficits. Limited studies have tested if GDM exposure is associated with higher autistic traits in typically developing children or what the neural substrates are. We used the social responsiveness scale (SRS) to measure differences in autistic traits between GDM-exposed and unexposed children and examined if white matter pathways involved in the social brain network (SBN) were related to autistic traits in children. Children were recruited from Kaiser Permanente Southern California to participate in BrainChild, a study assessing neural programming of disease risk (N=136; 9 ±1.5 years; 63% female; 52% GDM-exposed) . During visits, children completed a brain magnetic resonance imaging scan, demographics were collected, and parents completed the SRS. Maternal GDM diagnosis, glucose levels from a 1-hr 50g glucose challenge completed during pregnancy, and pre-pregnancy BMI were obtained from electronic medical records. Fractional anisotropy (FA) was used to assess white matter microstructure. Linear regression was used to test associations between SRS raw scores with GDM exposure, maternal glucose levels, and SBN white matter pathways, controlling for child age, sex, socioeconomic status, and maternal pre-pregnancy BMI. SRS scores were higher for GDM-exposed children than unexposed (GDM: 35.7±2.1; Unexposed: 29.5±2.3, p=0.03) . Maternal glucose levels were associated with higher child SRS scores (β=0.002, p=0.06) . Higher SRS scores were associated with reduced FA in multiple SBN white matter tracts (p<0.01) . GDM exposure and higher maternal glucose levels were associated with more autistic traits, suggesting that intrauterine exposure to a GDM hyperglycemic environment may affect autistic traits even among typically developing children. Further, SBN white matter tracts may be related to social deficits.
J.M.Alves: None. B.C.Angelo: None. S.Negriff: None. S.H.Luo: None. T.Chow: None. R.Cabeen: None. S.A.Carter: None. A.Xiang: None. K.A.Page: None.
pAmerican Diabetes Association (#1-14-ACE-36) ; R01DK116858