Effects of prenatal exposure to maternal diabetes mellitus on deep grey matter structures and attention deficit hyperactivity disorder symptoms in children

Aim: The neuronal mechanism linking the association between maternal diabetes mellitus (DM) and risk of attention deficit hyperactivity disorder (ADHD) symptoms and working memory deficits in children was investigated.

Methods: A total of 6291 children (52% boys) born beyond 28 weeks of gestation were included and underwent brain magnetic resonance imaging scans at 9-10 years. Subcortical brain volumes were estimated from the T1-weighted images. ADHD symptoms were assessed using factorial analysis of the Child Behaviour Checklist completed by parents/caregivers. Working memory performance was assessed with the NIH Toolbox.

Results: Compared to unexposed children, those exposed to DM (n = 422) had smaller (β = -0.15, p = 0.001) volumes of pooled deep grey matter (GM). Regional analysis revealed smaller volumes of the caudate nucleus, putamen, thalamus and cerebellum but not of hippocampus. They also had altered cortico-striatal white matter projection tracts. DM was not associated with working memory deficits or inattention, but with increased hyperactivity/impulsivity and Sluggish Cognitive Tempo symptoms in boys. This hyperactivity/impulsivity symptom in boys was partially mediated by smaller deep GM volume.

Conclusion: Exposure to DM during pregnancy leads to altered deep GM development during late childhood in their offspring. This contributed to an increased risk of hyperactivity/impulsivity symptoms in boys.