Selective morphological and volumetric alterations in the hippocampus of children exposed in utero to gestational diabetes mellitus

Abstract

Prior epidemiological studies have found that in utero exposure to gestational diabetes mellitus (GDM) is associated with increased risk for neurodevelopmental disorders. However, brain alterations associated with GDM are not known. The hippocampus is pivotal for cognition and emotional regulation. Therefore, we assessed relationships between in utero exposure to GDM and hippocampal morphology and subfield structure during childhood. One hundred seventeen children aged 7-11 years (57% girls, 57% exposed to GDM), born at Kaiser Permanente Southern California, participated in the BrainChild Study. Maternal GDM status was determined from electronic medical records. Children underwent brain magnetic resonance imaging. Freesurfer 6.0 was used to measure hippocampal and individual hippocampal subfield gray matter volume (mm 3 ). Morphological analyses on the hippocampal surface were carried out using shape analysis. GDMexposed children exhibited reduced radial thickness in a small, spatially-restricted portion of the left inferior body of the hippocampus that corresponds to the CA1 subfield. There was a significant interaction between GDM-exposure and sex on the right hippocampal CA1 subfield. GDM-exposed boys had reduced right CA1 volume compared to unexposed boys, but this association was no longer significant after controlling for age.No significant group differences were observed in girls. Our results suggest that GDMexposure impacts shape of the left hippocampal CA1 subfield in both boys and girls and may reduce volume of right hippocampal CA1 only in boys. These in-depth findings illuminate the unique properties of the hippocampus impacted by prenatal GDM-exposure and could have important implications for hippocampal-related functions.

Associations between prenatal exposure to gestational diabetes mellitus and child adiposity markers: mediating effects of brain structure

“…There were marginally significant findings that children prenatally exposed to maternal diabetes had smaller total surface area and total subcortical gray matter volume. Compared with previous studies [10][11][12] , ABCD study consisted of a larger and more diverse pediatric population across 21 sites in the US. The directionality of group differences were consistent with prior imaging studies [10][11][12] .…”

“…Compared with previous studies [10][11][12] , ABCD study consisted of a larger and more diverse pediatric population across 21 sites in the US. The directionality of group differences were consistent with prior imaging studies [10][11][12] . Effect sizes observed in brain outcomes were small yet comparable with other disorders observed in youth, such as attention deficit hyperactivity disorder, ASD, obsessive compulsive disorder, and major depressive disorder [35][36][37] .…”

“…It has been shown that levels of neurotrophins such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) – essential for neuronal growth, development, and differentiation – were lower in pregnant women with diabetes 8 or infants prenatally exposed to maternal diabetes 9 . Infants and youth prenatally exposed to maternal diabetes also demonstrated brain structural deficits, such as reduced hippocampal thickness 10 , reduced white matter integrity in sensorimotor regions 11 , and reduced cortical excitability 12 except for one study 13 .…”

“…Serum levels of neurotrophins including nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) – essential for neuronal growth, development, and differentiation – are lower in pregnant women with diabetes(21) and infants prenatally exposed to GDM(22). Offspring exposed to GDM prenatally demonstrated brain structural alterations, such as presence of hypothalamic gliosis, lower white matter integrity in sensorimotor regions(23), lower cortical excitability(24), and mixed results on the hippocampal thickness(25, 26). However, this work is hampered by small sample sizes and poor representation of diverse populations, calling into question the reproducibility and generalizability of findings.…”

Emotional Prosodies Processing and Its Relationship With Neurodevelopment Outcome at 24 Months in Infants of Diabetic Mothers

“…Abnormal maternal glucose metabolism during pregnancy leads to alterations in the intrauterine environment that can interfere with fetal brain development. Existing researches have found that the shape and volume of the hippocampus in IDM may be affected by intrauterine hyperglycemia ( 27 ). The hippocampus is a subcortical structure critical for learning, memory and emotion regulation ( 28 ), and hippocampus impairment may affect neurological function either directly or by breaking off neural connections.…”